Dedicated to Parents, Teachers&

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FORMULATION AND IN VITRO EVALUATION OF FAST DISSOLVING IMIPRAMINE HYDROCHLORIDE TABLETS

A Dissertation submitted to

THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI- 600 032

In partial fulfilment of the award of the degree of

MASTER OF PHARMACY IN

Branch-I -- PHARMACEUTICS

Submitted by

Name: MOSES RACHAN KUMAR.D REG.No.261810254

Under the Guidance of Mr. K. JAGANATHAN, M.Pharm.,

ASSOCIATE PROFESSOR DEPARTMENT OF PHARMACEUTICS

J.K.K. NATTARAJA COLLEGE OF PHARMACY KUMARAPALAYAM – 638183

TAMILNADU.

APRIL – 2020

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A Dissertation submitted to

THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI - 600 032

In partial fulfilment of the award of the degree of

MASTER OF PHARMACY IN

Branch-I -- PHARMACEUTICS Submitted by

Name: MOSES RACHAN KUMAR.D REG.No.261810254

Under the Guidance of Mr. K. JAGANATHAN, M.Pharm.,

ASSOCIATE PROFESSOR DEPARTMENT OF PHARMACEUTICS

J.K.K. NATTARAJA COLLEGE OF PHARMACY KUMARAPALAYAM – 638183

TAMILNADU.

APRIL – 2020

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CERTIFICATES

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This is to certify that the dissertation work entitled

“FORMULATION AND IN VITRO EVALUATION OF FAST DISSOLVING

IMIPRAMINE HYDROCHLORIDE TABLETS”, submitted by the student bearing REG.No.261810254 to “The Tamil Nadu Dr. M.G.R. Medical University – Chennai”, in partial fulfilment for the award of Degree of Master of Pharmacy in Pharmaceutics was evaluated by us during the

examination held on………..……….

Internal Examiner External Examiner EVALUATION CERTIFICATE

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This is to certify that the work embodied in this dissertation entitled

“FORMULATION AND IN VITRO EVALUATION OF FAST DISSOLVING

IMIPRAMINE HYDROCHLORIDE TABLETS”, submitted to “The Tamil Nadu Dr.

M.G.R. Medical University- Chennai”, in partial fulfilment and requirement of university rules and regulation for the award of Degree of Master of Pharmacy in Pharmaceutics, is a bonafide work carried out by the student bearing REG.No.261810254 during the academic year 2019-2020, under the guidance and supervision of Mr. K.JAGANATHAN, M.Pharm., Associate Professor, Department of Pharmaceutics, J.K.K. Nattraja College of Pharmacy, Kumarapalayam.

CERTIFICATE

Dr. R. Sambathkumar, M. Pharm., PhD., Professor & Principal,

Dr. S. Bhama, M. Pharm., PhD., Professor & HOD,

Department of Pharmaceutics Mr. K.Jaganathan, M.Pharm.,

Associate Professor,

Department of Pharmaceutics

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This is to certify that the work embodied in this dissertation

entitled “FORMULATION AND IN VITRO EVALUATION OF FAST OF DISSOLVING IMIPRAMINE HYDROCHLORIDE TABLETS”, submitted to “The Tamil Nadu Dr.

M.G.R. Medical University - Chennai”, in partial fulfilment and requirement of university rules and regulation for the award of Degree of Master of

Pharmacy in Pharmaceutics, is a bonafide work carried out by the student bearing REG.No.261810254 during the academic year 2019-2020, under my guidance and d ir ec t supervision in the Department of Pharmaceutics, J.K.K.

Nattraja College of Pharmacy, Kumarapalayam.

Place: Kumarapalayam Date:

CERTIFICATE

Mr. K. Jaganathan, M.Pharm., Associate Professor,

Department of Pharmaceutics

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This is to certify that the work embodied in this dissertation entitled “FORMULATION AND IN VITRO EVALUATION OF FAST OF DISSOLVING IMIPRAMINE HYDROCHLORIDE TABLETS”, submitted to “The Tamil Nadu Dr.

M.G.R. Medical University- Chennai”, in partial fulfilment and requirement of university rules and regulation for the award of Degree of Master of Pharmacy in Pharmaceutics, is a bonafide work carried out by the student bearing REG.No.261810254 during the academic year 2019-2020, under the guidance and supervision of Mr. K.Jaganathan, M.Pharm., Associate

Professor, Department of Pharmaceutics, J.K.K. Nattraja College of Pharmacy, Kumarapalayam.

Place: Kumarapalayam Date:

CERTIFICATE

Dr. R. Sambathkumar, M. Pharm., PhD., Professor & Principal,

J.K.K.Nattraja College of Pharmacy, Kumarapalayam.

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DECLARATON

I do hereby declared that the dissertation “FORMULATION AND IN VITRO EVALUATION OF FAST OF DISSOLVING IMIPRAMINE HYDROCHLORIDE TABLETS^”,

submitted to “The Tamil Nadu Dr. M.G.R Medical University - Chennai”, for the partial fulfilment of the degree of Master of Pharmacy in Pharmaceutics, is a bonafide research work has been carried out by me during the academic year 2019- 2020, under the guidance and supervision of Mr. K. Jaganathan, M.Pharm., Associate Professor, Department of Pharmaceutics, J.K.K. Nattraja College of Pharmacy, Kumarapalayam.

I further declare that this work is original and this dissertation has not been submitted previously for the award of any other degree, diploma,

associate ship and fellowship or any other similar title. The information furnished in this dissertation is genuine to the best of my knowledge.

Place: Kumarapalayam MOSES RACHAN KUMAR.D

Date: REG.No.261810254

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Dedicated to Parents, Teachers&

My Family

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ACKNOWLEDGEMENT

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ACKNOWLEDGEMENT

I am proud to dedicate my deep sense of gratitude to the founder, (Late) Thiru J.K.K. Nattaraja Chettiar, providing the historical institution to study.

My sincere thanks and respectful regards to our reverent Chairperson Smt. N. Sendamaraai, B.Com., and Director Mr. S. Omm Sharravana, B.Com., LLB., J.K.K. Nattraja Educational Institutions, Kumarapalayam for their blessings, encouragement and support at all times.

It is most pleasant duty to thank for our beloved Dr. R. Sambathkumar, M.Pharm., Ph.D., Principal & Professor,

Department of Pharmaceutics, J.K.K. Nattraja College of Pharmacy, Kumarapalayam for ensuring all the facilities were made available to me for the smooth running of this project and tremendous encouragement at each and every step of this dissertation work. Without his critical advice and deep-rooted knowledge, this work would not have been a reality.

It is my privilege to express deepest sense of gratitude toward Mr. K.Jaganathan, M.Pharm., Associate Professor, Department of Pharmaceutics, for their valuable suggestions and inspiration.

Our glorious acknowledgement to our administrative officer Dr. K. Sengodan, M.B.B.S., for encouraging using kind and generous manner to complete this work.

My sincere thanks to Dr. S. Bhama, M. Pharm., Ph.D., Professor & HOD, Department of Pharmaceutics, Mr. R. Kanagasabai, B.Pharm, M.Tech., Associate Professor, Dr. V. Kamalakannan M.

Pharm., Ph.D., Associate Professor, Mr. C. Kannan, M.Pharm., Assistant Professor, Ms. S. Manodhini Elakkiya, M.Pharm., Lecturer, Mr. M. Subramani, M.Pharm., Lecturer and Dr. Rosmi Jose, Pharm.D., Lecturer, Department of pharmaceutics for the in valuable help during my project.

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My sincere thanks to Dr. N. Venkateswaramurthy, M.Pharm., Ph.D., Professor and Head, Department of Pharmacy Practice,

Mrs. K. Krishna Veni, M.Pharm., Assistant Professor, Mr. R.

Kameswaran M.Pharm, Assistant Professor, Dr. Mebin Alias, Pharm.D., Assistant Professor, Mrs. P. J. Sujitha, Lecturer, Dr. Cindy Jose, Pharm.D., Lecturer, Dr. Krishna Ravi, Pharm.D., Lecturer, and Dr. S.K.Sumitha, Pharm.D., Lecturer, Department of Pharmacy Practice, for their help during my project.

It is my privilege to express deepest sense of gratitude toward Dr. M. Vijayabaskaran, M.Pharm., Ph.D., Professor & Head, Department of Pharmaceutical chemistry, Mrs. B. Vasuki, M.Pharm., Assistant Professor and Ms. P. Lekha, Lecturer for their valuable suggestions and inspiration.

My sincere thanks to Dr. V. Sekar, M.Pharm., Ph.D., Professor and Head, Department of Analysis, Dr. I. Caolin Nimila, M.Pharm., Ph.D., Assistant Professor, Mr. D. Kamalakannan Assistant Professor, Mrs. P. Devi, M.Pharm., Lecturer and Ms. V. Devi, M.Pharm., Lecturer, Department of Pharmaceutical Analysis for their valuable suggestions.

My sincere thanks to Dr. Senthilraja, M.Pharm., Ph.D., Associate Professor and Head, Department of Pharmacognosy, Mrs. P.Meena Prabha, M.Pharm., Lecturer, Department of Pharmacognosy and Mr. Nikhil.P.S, M.Pharm., Lecturer, Department of Pharmacognosy for their valuable suggestions during my project work.

My sincere thanks to Dr. R. Shanmugasundaram, M.Pharm., Ph.D., Vice Principal & HOD, Department of Pharmacology,

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Dr. C. Kalaiyarasi, M.Pharm., Ph.D., Associate Professor, Mr. V. Venkateswaran, M.Pharm., Assistant Professor, Mrs. M. Sudha M.Pharm., Lecturer, Mr. T. Thiyagarajan, M.Pharm., Assistant Professor, Mrs. R. Elavarasi, M.Pharm., Lecturer, Mrs. M. Babykala, M.Pharm., Lecturer, and Mrs. P.J.

Sujitha, M.Pharm., Lecturer, Department of Pharmacology for their valuable suggestions during my project work.

I greatly acknowledge the help rendered by Mrs. K. Rani, Office Superintendent, S. Sudhalakshmi, Typist, Mrs. V. Gandhimathi, M.A., M.L.I.S., Librarian, Mrs. S. Jayakala B.A., B.L.I.S., and Asst.

Librarian for their co-operation. I owe my thanks to all the technical and non-technical staff members of the institute for their precious assistance and help.

Last, but nevertheless, I am thankful to my lovable parents and all my friends for their co-operation, encouragement and help extended to me throughout my project work.

MOSES RACHAN KUMAR.D

REG.No.261810254

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CHAPTER 1 INTRODUCTION

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CHAPTER 2 LITERATURE

REVIEW

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CHAPTER 3 AIM AND OBJECTIVE

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CHAPTER 4 PLAN OF WORK

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CHAPTER 5 DISEASE PROFILE

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CHAPTER 6 DRUG PROFILE

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CHAPTER 7 EXCIPIENT PROFILE

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CHAPTER 8 MATERIALS AND

EQUIPMENTS

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CHAPTER 9 PREFORMULATION

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CHAPTER 10 FORMULATION

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CHAPTER 11 EVALUATION

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CHAPTER 12 RESULTS AND

DISCUSSION

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CHAPTER 13 SUMMARY AND

CONCLUSION

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CHAPER 14

BIBILOGRAPHY

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Formulation And In Vitro Evaluation Of Fast Dissolving Imipramine Hydrochloride Tablets

DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY

FORMULATION AND IN VITRO EVALUATION OF FAST DISSOLVING IMIPRAMINE HYDROCHLORIDE

TABLETS

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY LIST OF ABBREVIATIONS

Abs.

BCS CCS Conc.

DSC DT

Absorbance

Biopharmaceutical classification system Croscarmellose sodium

Concentration

Differential scanning calorimetry Disintegration time

F1 Difference factor

F2 FDT FDDDS

Similarity factor Fast dissolving tablet

Fast dissolving drug delivery system FT-IR Fourier transform infrared spectroscopy GIT

HCl IP

Gastrointestinal tract Hydrochloric acid Indian pharmacopoeia

LBD Loose bulk density

MCC mg ml µg nm

Microcrystalline cellulose milligram

milliliter microgram nanometer

RH Relative humidity

rpm Rotations per minute

SD SS SSG TBD UV USP W/V WT

Standard deviation Stock solution

Sodium starch glycolate Tapped bulk density Ultraviolet

United states pharmacopoeia Weight/volume

Wetting time

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SL Nos. Chapters Page No.

1. Introduction 1-15

2. Review of Literature 16-24

3. Aim and Objectives 25-26

4. Drug and excipient profile 27-46

5.

6.

7.

Methodology

Results and Discussion

Conclusion

47-64 65-97

98-99

8. Bibliography 100-105

LIST OF CONTENTS

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Sl. No. Tables Page

No.

Table 1 Data for calibration curve of imipramine hydrochloride in phosphate buffer (pH 6.8) solution

51

Table 2 Data for calibration curve of imipramine hydrochloride in 0.1 N hydrochloric acid solution

53

Table 3 Comparison between angle of repose and flow properties 56 Table 4 Grading of the powders for their flow properties according to Carr’s

Index

57

Table 5 Formulations of imipramine hydrochloride tablets 59 Table 6 Comparison of the peak of functional groups observed in IR spectra

of compatibility studies.

72

Table 7 Physical parameters of drug and polymers 77

Table 8 Physical properties of the powder-blends of the batches F1 and F2 79 Table 9 Properties of the fast dissolving tablets for the batches F1 and F2 79 Table 10 In vitro release of imipramine HCl from tablets of F1 and F2 80 Table 11 Physical properties of the powder-blends of the batches F3 and F4 81

Table 12 Properties of the matrix tablets for the batches F3 and F4 82 Table 13 In vitro release of imipramine HCl from tablets of F3 and F4 83 Table 14 Properties of the fast dissolving tablets for the batches F5 and F6 84 Table 15 Properties of the fast dissolving tablets for the batches F5 and F6 85

LIST OF TABLES

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Sl. No. Tables Page

No.

Table 16 In vitro release of imipramine HCl from tablets of F5 and F6 86 Table 17 Physical properties of the powder-blends of the batches F7 and F8 87

Table 18 Properties of the fast dissolving tablets for the batches F7 and F8 88

Table 19 In vitro release of imipramine HCl from tablets of F7 and F8 89 Table 20 Data for the in vitro release of imipramine hydrochloride from the

tablets of the batch F8 and reproducible batch in phosphate buffer solution, pH 6.8.

92

Table 21 Comparison of f1 and f2 values for the tablets of the batch F8 and reproducible batch

93

Table 22 Characterization of the Marketed Tablet 94

Table 23 In vitro % drug release for the FDT batch F8 and Marketed Product

94 Table 24 Evaluations for Physical Appearance after Stability Studies of FDT

of batch F8

96 Table 25 Evaluation for Percentage Drug Content, Hardness, and In vitro

Dispersion Time after Stability Studies of FDT of batch F8

96

Table 26 Evaluation for In vitro Drug Release Profile for FDT Formulations of after Imipramine hydrochloride Stability Studies

96

Table 27 Comparison of f1 and f2 values for the tablets of the batches F8for 15 and 30 days

97

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Sl. No. Figures Page

No.

Figure 1 UV spectrum of imipramine hydrochloride in phosphate buffer (pH 6.8) Solution

50

Figure 2 Calibration curve of imipramine hydrochloride in phosphate buffer (pH 6.8) solution

51

Figure 3 UV spectrum of imipramine hydrochloride in 0.1N HCl Solution 52 Figure 4 Calibration curve of imipramine hydrochloride in 0.1N

hydrochloric acid solution

53

Figure 5 UV spectrum of imipramine HCl and croscarmellose sodium 66 Figure 6 UV spectrum of imipramine HCl and agar 66 Figure 7 UV spectrum of imipramine HCl and gum karaya 67 Figure 8 UV spectrum of imipramine HCl and plantago ovata 67 Figure 9 UV spectrum of imipramine HCl and Pearlitol SD - 200 68 Figure 10 UV spectrum of imipramine HCl and microcrystalline cellulose 68

Figure 11 DSC of Imipramine hydrochloride 70

Figure 12 DSC of Dummy formula (formulation F8) 70

Figure 13 DSC of optimized formula F8 71

Figure 14 FT-IR spectrum of pure imipramine HCl 73 Figure 15 FT-IR spectrum of imipramine HCl and croscarmellose sodium 73

LIST OF FIGURES

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Sl. No. Figures Page

No.

Figure 16 FT-IR spectrum of imipramine HCl and agar 74 Figure 17 FT-IR spectrum of imipramine HCl and gum karaya 74 Figure 18 FT-IR spectrum of imipramine HCl and plantago ovata 75 Figure 19 FT-IR spectrum of imipramine HCl and Pearlitol SD 200 75 Figure 20 FT-IR spectrum

cellulose

of imipramine HCl and Microcrystalline 76

Figure 21 FT-IR spectrum of optimize formula 76

Figure 22 In vitro release of imipramine hydrochloride from the tablets of the batches F1 and F2

80

Figure 23 In vitro release of imipramine hydrochloride from tablets of batches F3 and F4

83 Figure 24 In vitro release of Imipramine hydrochloride from the tablets of

batches F5 to F6

86

Figure 25 In vitro release of imipramine hydrochloride from tablets of batches F7 and F8

90

Figure 26 In vitro release of imipramine hydrochloride from the tablets of the batch F8 and reproducible batch

92

Figure 27 Comparison of In vitro drug release of imipramine hydrochloride with marketed product and formulation F8

95

Figure 28 In vitro releases of Imipramine hydrochloride FDT tablets from F8

on zero day, after 15 days and after month of accelerated stability studies

97

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Formulation And In Vitro Evaluation Of Fast Dissolving Imipramine Hydrochloride Tablets

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FORMULATION AND IN VITRO EVALUATION OF FAST DISSOLVING IMIPRAMINE HYDROCHLORIDE TABLETS

DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 1

1.INTRODUCTION

Oral drug delivery has been known for decades as the most widely utilized route of administration among all the routes that have been explored for the systemic delivery of drugs via various pharmaceutical products of different dosage forms. The reason that the oral route achieved such popularity may be attributed to its ease of administration as well as the traditional belief that by oral administration the drug is well absorbed as the food stuffs ingested daily.¹

Oral route of drug administration has wide acceptance up to 50-60% of total dosage forms. Solid dosage forms are popular and most preferred route due to its advantages because of ease of administration, accurate dosage, self-medication, pain avoidance, and most importantly the patient compliance. The most popular solid dosage forms are being tablets and capsules. One important drawback of these dosage forms for some patients however is difficult to swallow.² Recent market studies indicate that more than half of the patient population prefers FDTs to other dosage forms and most consumers would ask their doctors for FDTs (70%), purchase FDTs (70%), or prefer FDTs to regular tablets.³

Drinking water plays an important role in the swallowing of oral dosage forms. Often times people experience inconvenience in swallowing conventional tablets and capsules, when water is not available, in case of motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic conditions, and bronchitis.⁴ For these reasons, tablets which can fast dissolve or disintegrate in the oral cavity have attracted a great deal of attention. Fast dissolving or disintegrating tablets are not only indicated for people who have swallowing difficulties, but also are ideal for everyone.⁵

There are several factors other than physicochemical properties of the drug that may influence the

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 2 dissolution rate of the solid dosage forms. It has shown that, the dissolution rate of pure drugs can be altered significantly by the proper selection of formulation components as well as processing methods.⁶

Fast dissolving tablets are gaining prominence as new drug delivery systems. These dosage forms dissolve or disintegrate in oral cavity within a minute without the need of water.

These are useful in administration of drugs in pediatric and geriatric patients and also in patients suffering from dysphagia, leading to improved patient compliance. Several approaches have been employed to formulate fast dissolving tablets which involve the techniques like tablet molding, increasing porosity by freeze drying, sublimation, drying, disintegrants addition and use of sugar excipients.⁷

Fast dissolving tablets are also called mouth dissolving tablets, oro-dispersible tablets, melt-in-mouth tablets, rapimelts, porous tablets, rapidly dissolving tablets, or rapidly disintegrating tablets.

Fast dissolving tablets are those when put on tongue, disintegrates instantaneously, releasing the drug, which dissolves or disperses in the saliva. FDTs release drug in the mouth for absorption through local oromucosal tissues and through pregastric (e.g., oral cavity, pharynx, and esophagus), gastric (i.e., stomach), and postgastric (e.g., small and large intestines) segments of the gastrointestinal tract (GIT).³

The faster the drug undergoes into solution, the quicker the absorption and rapid onset of action. Some drugs are absorbed from the mouth, pharynx, and oesophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablet dosage form. The bioavailability of some drugs may be increased due to absorption of drug in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into the stomach. More ever, the amount of

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 3 drug that is subjected to first pass metabolism is reduced as compared to standard tablet. The advantages of fast dissolving dosage forms are increasingly being recognized in both, industry and academics. Their growing importance was underlined recently when European Pharmacopoeia adopted the term “orodispersible tablet” as a tablet that to be placed in the mouth where it disperses rapidly before swallowing.⁸

United States Food and Drug Administration (FDA) defined ODT as “A solid dosage form containing medicinal substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed upon the tongue.” The disintegration time for ODTs generally ranges from several seconds to about a minute.

FDT products have been developed for numerous indications ranging from migraines (for which a rapid onset of action is important) to mental illness (for which patient compliance is important for treating chronic indications such as depression and schizophrenia).⁷

Criteria’s for fast dissolving Drug Delivery System: ⁹ Fast dissolving tablets should:

 not require water to swallow, but it should dissolve or disintegrate in the mouth in a matter of seconds.

 have a pleasing mouth feel.

 be compatible with taste masking.

 be portable without fragility concern.

 leave minimal or no residue in the mouth after oral administration.

 exhibit low sensitivity to environmental conditions such as humidity and temperature.

 allow the manufacture of tablet using conventional processing and packaging equipment at low cost.

Advantages of fast dissolving tablets: ¹²

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 Ease of administration to patients who refuses to swallow a tablet such as pediatrics, geriatric patients, and psychiatric patients.

 No need or little water is required to swallow the dosage form which is highly convenient feature for patients who are traveling and do not have access to water.

 Free of risk of suffocation due to physical obstruction when swallowed, thus offering improved safety.

 Rapid disintegration and absorption of drug, which will produce quick onset of action.

 Quick absorption from the gastro intestinal tract improves bioavailability and reduces unwanted effects caused by the drugs and also improves patient compliance.

 New business opportunities like product differentiation, line extension, and life cycle management. Exclusivity of product promotion.

 Patients for whom chewing is difficult or painful can use these new tablets easily. Fast dissolving tablets can be used easily in children who have lost their primary teeth, but do not have full use of their permanent teeth.

Disadvantages of fast dissolving tablets: ¹³

 In most cases the fast dissolving tablets lack the mechanical strength common to traditional tablets. Many products are very lightweight and fragile requiring them to be individually packaged. Patients should be advised not to push these tablets through the foil film, but instead, peel the film back to release the fast-dissolving tablet.

 Due to the formulation of fast dissolving tablets, which are also more susceptible to degradation via temperature and humidity, some of the newer fasts dissolving tablet formulations are dispensed in a conventional stock bottle. Pharmacists are advised to take care when dispensing such formulations to ensure they are not exposed to high

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 5 levels of moisture or humidity. Excess handling of tablets can introduce enough moisture to initiate dissolution of tablet matrix.

Salient Features of fast dissolving Drug Delivery System: ⁹

 Ease of administration to patients who refuse to swallow a tablet such as, pediatric, geriatric patients and psychiatric patients.

 Convenience of administration and accurate dosing as compared to liquids.

 No need of water to swallow the dosage form, which is highly convenient especially for patients who are traveling and do not have immediate access to water.

 Good mouth feel property of MDDS helps to change the basic view of medication as

“bitter pill”, particularly for pediatric patients.

 Rapid dissolution and absorption of drug, which may produce quick onset of action.

 Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach; in such cases bioavailability of drugs is increased.

 Ability to provide advantages of liquid medication in the form of solid form.

 Pregastric absorption can result in improved bioavailability and as a result of reduced dosage, improved clinical performance through a reduction of unwanted effects.

Ideal characteristics of a drug for fast dissolving tablets: ¹⁰

 No bitter taste.

 Dose lower than 20 mg.

 Small to moderate molecular weight.

 Good solubility in water and saliva.

 Partially nonionized at the oral cavity's pH.

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 Ability to diffuse and partition into the epithelium of the upper GIT (log P >1, or preferably >2).

 Ability to permeate oral mucosal tissue (15).

Challenges to Develop FDT: ¹¹

 Rapid disintegration of tablet

 Avoid increase in tablet size

 Have sufficient mechanical strength

 Minimum or no residue in mouth

 Protection from moisture

 Good package design

 Compatible with taste masking technology

 Not affected by drug properties

Techniques for Preparing Mouth Dissolving Tablets: ^9,^12,¹⁴

Various technologies used in the manufacture of mouth dissolving tablets include:

1. Freeze drying/ lyophillization 2. Molding

3. Cotton – candy process 4. Spray drying

5. Mass extrusion 6. Compaction

a. Melt granulation

b. Phase transition process c. Sublimation

d. Conventional methods

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 7 i. Dry granulation

ii. Wet granulation iii. Direct compression

 Disintegrant addition

 Sugar based excipients

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 8 Freeze Drying

A process in which water is sublimated from the product after freezing is called freeze drying. Freeze dried forms offer more rapid dissolution than other available solid products.

The lyophillization process imparts glossy amorphous structure to the bulking agent and sometimes to the drug, thereby enhancing the dissolution characteristics of the formulation.

However, the use of freeze drying is limited due to high cost of the equipment and processing.

Other major disadvantages of the final dosage forms include lack of physical resistance in standard blister packs.

A tablet that rapidly disintegrates in aqueous solution includes a partially collapsed matrix network that has been vacuum dried above the collapse temperature of the matrix. The matrix is partially dried below the equilibrium freezing point of the matrix. Vacuum drying of the tablet above its collapse temperature instead of freeze drying below its collapse temperature provides a process for producing tablets with enhanced structural integrity, while rapidly disintegrating in normal amounts of saliva.

Moulding

Tablets produced by moulding are solid dispersions. Physical form of the drug in the tablets depends on to what extent it dissolves in the molten carrier. The drug can exist as discrete particles or microparticles dispersed in the matrix. It can dissolve totally in the molten carrier to form solid solution or dissolve partially in the molten carrier and the remaining particles stay undissolved and dispersed in the matrix. Disintegration time, drug dissolution rate and mouth feel will depend on the type of dispersion or dissolution. Moulded tablets disintegrate more rapidly and offer improved taste because the dispersion matrix is, generally made from water-soluble sugars. Moulded tablets typically do not possess great mechanical strength.

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 9 Erosion and breakage of the moulded tablet often occur during handling and opening of blister packs.

Sublimation

Because of low porosity, compressed tablets composed of highly water-soluble excipients often do not dissolve rapidly in the water. Porous tablets that exhibit good mechanical strength and dissolve quickly have been developed. Inert solid ingredients (E.g.

urea, urethane, ammonium carbonate, camphor, naphthalene) were added to other tablet excipients and the blend was compressed into tablet. Removal of volatile material by sublimation generated a porous structure. Compressed tablets containing mannitol and camphor have been prepared by sublimation technique. The tablets dissolve within 10-20 seconds and exhibit sufficient mechanical strength for practical use.

Spray Drying

Highly porous and fine powders can be produced by spray drying, as the processing solvent is evaporated rapidly during spray drying. Spray drying technique is based upon a particulate support matrix and other components to form a highly porous and fine powder. This is then mixed with above ingredient and compressed to tablet. The fast dissolving tablets prepared from Spray drying technique disintegrated within 20 seconds.

Mass Extrusion

This technology involves softening the active blend using the solvent mixture of water- soluble polyethylene glycol, using methanol and expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets. The dried cylinder can also be used to coat granules of bitter tasting drugs and thereby making their bitter taste.

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 10 Direct Compression

It is the easiest way to manufacture tablets. Conventional equipment, commonly available excipients and a limited number of processing steps are involved in direct compression. Also high doses can be accommodated and final weight of tablet can easily exceed that of other production methods. Directly compressed tablet’s disintegration and solubilization depends on single or combined action of disintegrants, water-soluble excipients and effervescent agent. Disintegrant efficacy is strongly affected by tablet size and hardness.

Large and hard tablets have disintegration time more than that usually required. As consequences, products with optimal disintegration properties often have medium to small size and/or high friability and low hardness. Breakage of tablet edges during handling and tablet rupture during the opening of blister alveolus, all result from insufficient physical resistance.

Patented Technologies for Orodispersible or Mouth Dissolving Tablets: ^9,¹⁵

Zydis technology: Zydis is patented by R.P. Schere. This technology includes physical trapping of the drug in a matrix composed of a saccharide and a polymer. Polymers generally employed are partially hydrolyzed gelatin, hydrolyzed dextran, dextrin, alginates, polyvinyl alcohol, polyvinyl pyrrolidine, acacia, and these mixtures. The methodology involves solution or dispersion of components is prepared and filled in a liquid nitrogen environment. The frozen solvent is removed or sublimed to produce porous wafers. Peelable backing foil is used to pack Zydis units. Zydis formulation is sensitive to moisture and may degrade at humidity greater than 65%.

Desired characteristics of Zydis technology I. Drug should be chemically stable II. Water insoluble

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 11 III. Particle size should be smaller than 50 µm

IV. Dose for water soluble drugs is limited (60 mg)

Lyoc: Lyoc technology is patented by PHARMALYOC. Oil in water emulsion is prepared and placed directly in to blister cavities followed by freeze drying. Nonhomogeneity during freeze drying is avoided by incorporating inert filler to increase the viscosity finally the sedimentation. High proportion of filler reduces porosity of tablets due to which disintegration is lowered.

Quick solv: This technology is patented by Janssen Pharmaceutical. It utilizes two solvents in formulating a matrix, which disintegrates instantly. Methodology includes dissolving matrix components in water and the solution or dispersion is frozen. Then dry the matrix by removing water using an excess of alcohol (solvent extraction). Thus the product formed has uniform porosity and adequate strength for handling.

Nanocrystal technology: This is patented by Elan, King of Prussia. Nanocrystal technology includes lyophillization of colloidal dispersions of drug substance and water soluble ingredients filled in to blister pockets. This method avoids manufacturing process such as granulation, blending, and tableting, which is more advantageous for highly potent and hazardous drugs. As manufacturing losses are negligible, this process is useful for small quantities of drug.

Flashtab technology: This is patented by Ethypharm, France. This technology includes granulation of excipients by wet or dry granulation method followed by compressing into tablets. Excipients used in this technology are of two types. Disintegrating agents include polyvinyl pyrrolidine or Carboxymethyl cellulose. Swelling agents include Carboxymethyl cellulose, starch, modified starch, microcrystalline cellulose, Carboxy methylated starch, etc.

these tablets have satisfactory physical resistance. Disintegration time is within 1 min.

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 12 Orasolv technology: This technology is patented by CIMA Labs. This includes use of effervescent disintegrating agents compressed with low pressure to produce the ODT. The evolution of carbon dioxide from the tablet produces fizzing sensation, which is positive organoleptic property. Concentration of effervescent mixture usually employed is 20-25% of tablet weight.

As tablets are prepared at low compression force, they are soft and fragile in nature.

This initiated to develop Paksolv, a special packaging to protect tablets from breaking during storage and transport. Paksolv is a dome shaped blister package, which prevents vertical movement of tablet within the depression. Paksolv offers moisture, light, and child resistance packing.

Durasolv technology: This technology is patented by CIMA Labs. The tablets produced by this technology utilize the conventional tableting equipment. Tablets in this are formulated by using drug, no direct compression fillers, and lubricants.

Noncompressible fillers are dextrose, mannitol, sorbitol, lactose, and sucrose, which have advantage of quick dissolution avoid gritty texture, which is generally present in direct compressible sugar. The tablets obtained are strong and can be packed in conventional packing in bottles and blisters. No direct compressible fillers generally used in the range of 60-95%, lubricant in 1-2.5%.

WOW tab technology: Yamanouchi patented this technology. WOW means without water. This technology utilizes conventional granulation and tableting methods to produce FDT employing low- and high- molding saccharides.

Low- moldability saccharides are lactose, mannitol, glucose, sucrose, and xylitol. High- moldability saccharides are maltose, maltitol, sorbitol, and oligosaccharides. When these low- and high- moldable saccharides used alone, tablets obtained do not have desired properties

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 13 of rapid disintegration and hardness, so combinations are used. This technology involves granulation of low- moldable saccharides with high- moldable saccharides as a binder and compressing into tablets followed by moisture treatment. Thus tablets obtained showed adequate hardness and rapid disintegration.

Dispersible tablet technology: Lek, Yugoslavia patents this technology. It offers development of ODT with improved dissolution rate by incorporating 8-10% of organic acids and disintegrating agents. Disintegrating agents facilitates rapid swelling and good wetting capabilities to the tablets that results in quick disintegration.

Disintegrants include starch, modified starches, microcrystalline cellulose, alginic acid, crossed-link sodium Carboxy methyl cellulose and cyclodextrin. Combination of disintegrant improved disintegration of tablets usually less than 1 min.

Pharmaburst technology: SPI Pharma, New Castle, patents this technology. It utilizes the coprocessed excipients to develop ODT, which dissolves within 30-40 seconds. This technology involves dry blending of drug, flavor, and lubricant followed by compression into tablets. Tablets obtained have sufficient strength so they can be packed in blister pack sand bottles.

Frosta technology: Akina patents this technology. It utilizes the concept of formulating plastic granules and compressing at low pressure to produce strong tablets with high porosity.

Plastic granules composed of:

 Porous and plastic material

 Water penetration enhancer, and

 Binder

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 14 The process involves usually mixing the porous plastic material with water penetration enhancer and followed by granulating with binder. The tablets obtained have excellent hardness and rapid disintegration time ranging from 15 to 30 seconds depending on size of the tablet.

Oraquick: This technology is patented by K.V.Pharmaceuticals. It utilizes taste masking microsphere technology called as micromask, which provides superior mouth feel, significant mechanical strength, and quick disintegration/dissolution of product. This process involves preparation of microparticles in the form of matrix that protects drug, which can be compressed with sufficient mechanical strength. Low heat of production in this process makes it appropriate for heat sensitive drugs. Oraquick product dissolves within few seconds.

Ziplets/advatab: This technology is patented by Pessano con Bornago, Italy. It utilizes water insoluble ingredients combined with one or more effective disintegrant to produce ODT with improved mechanical strength and optimal disintegration time at low compression force.

This technology handles high drug loading and coated drug particles and does not require special packaging, so they can be packed in push through blisters or bottles.

Flashdose: Fuisz has patented flashdose technology. Nurofen meltet, a new form of ibuprofen as melt-in-mouth tablets, prepared using flashdose technology is the first commercial product launched by Bioavail Corporation. Flashdose tablets consist of self binding Shearform matrix termed as “floss”. Shearform matrices are prepared by flash heat processing.

Ceform technology: In this, microspheres containing active ingredient are prepared. The manufacturing process involves placing a dry powder, containing either substantially pure drug material or a special blend of drug materials plus other pharmaceutical compounds, and excipients into precision engineered, and rapidly spinning machine. The centrifugal force

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 15 throws dry blend at high speed through small, heated openings. The resultant microburst of heat liquefies the drug blend to form sphere. The microspheres are blended or compressed into preselected oral delivery dosage form. The microspheres can be incorporated into a wide range of fast dissolving dosage forms such as flash dose, or spoon dose, EZ chew.

Shearform technology: Shearform technology is based on preparation of floss that is also known as “Shearform Matrix”, which is produced by subjecting a feedstock containing a sugar carrier to flash heat processing. In this process, the sugar is simultaneously subjected to centrifugal force and to a temperature gradient, which raises the temperature of the mass to create an internal flow condition, which permits part of it to move with respect of the mass.

The flowing mass exits through the spinning head that flings the floss. The floss so produced is amorphous in nature so it is further cropped and recrystallised by various techniques to provide uniform flow properties and then facilitates blending. The recrystallised matrix is then blended with other tablet excipients and an active ingredient. The resulting mixture is compressed into tablet. The active ingredient and other excipients can be blended with floss before carrying out recrystallisation. The Shearform floss, when blended with the coated or uncoated microspheres, is compressed into tablets or EZ chewable tablets from standard tableting equipment.

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2.REVIEW OF LITERATURE

The review of literature revealed that a number of studies have been carried out on mouth dissolving tablets using different techniques which are as follows:

Schiermeier S et al., (2002)¹⁶ mentioned fast dispersible tablets disintegrate either rapidly in water, to form a stabilized suspension, or disperse instantaneously in the mouth to be swallowed without the aid of water. A direct compression method was used to prepare these two types of tablets containing coated ibuprofen as a high dosed model drug to develop an orodispersible tablet, a rotatable central composite design was applied to predict the effects of the quantitative factors mannitol and crospovidone as well as compression force on the characteristics of the tablet.

Shishu et al., (2007)¹⁷ prepared rapidly disintegrating tablets of chlorpheniramine maleate using taste masked granules. The taste masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. in vitro release profile obtained at pH 6.8 indicate that perceivable amount of drug will not be released in saliva while high percent release (more than 80% in 30 min) would be obtained at acidic pH 1.2 of the stomach. These taste masked granules were directly compressed into tablets using sodium starch glycolate as a super disintegrant.

Malke S et al., (2007)¹⁸ fast dissolve tablets of oxcarbazepine were prepared containing Avicel PH 102 as a diluent and Ac-Di-Sol as a superdisintegrants by wet granulation process. A modified disintegration method was used for studying disintegration.

Since the drug is poorly water soluble, drug release was tested in various media and the effect of surfactant on drug release was studied.

Madgulkar AR et al., (2007)¹⁹ studied the efficacy of Indion 414 and Amberlite IRP

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 17 88 as superdisintegrants in mouth dissolve tablets of Nimesulide. Formulations alsocontain camphor.Tablets were prepared by wet granulation method. The compressedtabletswere stored at 50°C for two hours to bring about sublimation of camphor. The tablets were evaluated for parameters like hardness, friability, weight variation, drug content, in vitro dispersion time, in vivo dispersion time and drug release. Indion 414 was found best compared to Amberlite IRP 88.

Swamy PV et al., (2007)²⁰ designed orodispersible tablets of meloxicam with a view to enhancepatient compliance. A combination of superdisintegrants i.e., sodium starch glycolate- crospovidone and sodium starch glycolate-croscarmellose sodium were used with directly compressible mannitol to enhance mouth feel. Based on in vitro dispersion time (approximately 10 sec), two formulations (one from each batch) were tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short term stability (at 45°C for 3 weeks) and drug-excipients interaction (IR spectroscopy). Among the two formulations, the formulation containing 2% w/w/ sodium starch glycolate and 1.5% w/w croscarmellose sodium was found to be better formulation.

Sharma S et al., (2008)²¹ prepared fast dissolving tablets of promethazine theoclate by direct compression after incorporating superdisintegrants Ac-Di-Sol, sodium starch glycolate, and crospovidone in different concentrations. Different types of evaluation parameters for tablets were used. Tablets containing Ac-Di-Sol showed superior organoleptic properties, along with excellent in vitro and in vivo dispersion time and drug release, as compared to other formulations.

Patel DM et al., (2008)²² developed fast dissolving tablets of etoricoxib; a 3² full factorial design was applied to investigate the combined effect of 2 formulation variables:

amount of menthol and crospovidone. Granules containing etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique. Menthol was sublimed

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 18 from the granules by exposing the granules to vacuum. The porous granules were then compressed in to tablets. Alternatively, tablets were first prepared and later exposed to vacuum. The result of multiple regression analysis indicated that for obtaining fast dissolving tablets; optimum amount of menthol and higher percentage of crospovidone should be used.

Setty CM et al., (2008)²³ prepared aceclofenac fast dispersible tablets by direct compression method using different superdisintegrants, croscarmellose sodium, sodium starch glycolate, and crospovidone and their effect on wetting time, disintegration time, drug content, in vitro release and stability parameters had been studied. Disintegration time and dissolution parameters decreased with increase in the level of croscarmellose sodium. Whereas, disintegration time and dissolution parameters increased with increase in the level of sodium starch glycolate in tablets. However the disintegration time values did not reflect in the dissolution parameter values of crospovidone tablets and release was dependent on the aggregate size in the dissolution medium.

Mundada AS et al., (2008)²⁴ developed a technique to mask the bitter taste of roxithromycin by complexation technique and prepared dispersible tablet of taste masked granules. Weak cation exchange resins Indion 214 and Amberlite IRP 64, polymer carbopol 934 P were used in formulation of complexes with the drug. The loading process was optimized for the pH loading solution and resin or polymer: drug ratio. The complexes were evaluated for bulk density, angle of repose, taste masking, and in vitro drug release. Amberlite IRP 64 was found to be better complexing agent for masking bitter taste of roxithromycin.

Mulla JA et al., (2008)²⁵ developed fast dissolving tablets of promethazine hydrochloride using direct compression after incorporating superdisintegrants such as Ac-Di- Sol, Explotab, and Polyplasdone XL in different concentrations. The prepared tablets were evaluated for different pharmacopoeial tests. Tablets containing Ac-Di-Sol showed better

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 19 disintegrating character along with rapid release.

Mohapatra A et al., (2008)²⁶ developed orally disintegrating tablets of metformin hydrochloride using direct compression and wet granulation method. Tablets prepared with direct compression using starch 1500 and microcrystalline cellulose showed erosion behavior rather than disintegration and also did not give good mouth feel. Thus Pearlitol SD 200 (spray dried mannitol) was used to prepare tablets by wet granulation (10% PVP in IPA as binder).

The strong saline and slight bitter taste of the drug was masked using nonnutritive sweetener andflavor.

Furtado S et al., (2008)²⁷ Orodispersible tablets of famotidine were prepared using

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 20 camphor as subliming agent and sodium starch glycolate together with crosscarmellose sodium as superdisintegrants. The formulations were evaluated for weight variation, hardness, friability, drug content, wetting time, in vitro and in-vivo dispersion, mouth feel and in vitro dissolution. All the formulations showed low weight variation with dispersion time less than 30 seconds and rapid in vitro dissolution. The results revealed that the tablets containing subliming agent had a good dissolution profile.

Singh J et al., (2008)²⁸ optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non- aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2³ factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate are desirable for orodispersion.

Mahapatra A et al., (2009)²⁹ develop and characterize mouth dissolving tablets of Levocetirizine hydrochloride using sublimation technique. Mouth dissolving tablets of Levocetirizine hydrochloride using different concentrations of Pearlitol SD 200 (spray dried mannitol) and menthol were developed using direct compression technique. The technique is to increase the porosity of the tablets whereby menthol, a subliming material was removed by sublimation from compressed tablets. A high porosity was achieved due to the formation of

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 21 many pores where menthol particles previously existed in the compressed tablets prior to sublimation of the menthol. Along with usual physical properties, the wetting time of tablets also measured. In-vitro and in vivo disintegration time of tablets were determined.

Kawtikwar P.S et al., (2009)³⁰ prepare bitter less fast dissolving tablet of Tizanidine Hydrochloride using Eudragit E 100 as a taste masking agent. Mass extrusion was the technique used for preparing taste masked granules. The tablet was prepared with three super disintegrates e.g. sodium starch glycolate, crosscarmellose sodium and crospovidone. The blend was examined for angle of repose, bulk density, tapped density and hausner ratio. The tablets were evaluated for hardness, drug content and friability and disintegration time. The disintegration in oral cavity was also tested and was found to be 22 sec. Other tablets were prepared by using camphor as sublimating agent. It was concluded that tablets prepared by addition of superdisintegrant has less disintegration time than those prepared by sublimation method.

Modasiya M.K et al., (2009)³¹ prepare fast disintegrating tablets of Piroxicam in the oral cavity with enhanced dissolution rate. The tablets were prepared with three super disintegrates sodium starch glycolate, Ac-Di-Sol and low molecular weight hydoxy propyl methylcellulose. The blend was examined for angle of repose, bulk density, tapped density, compressibility index and Hausner’s ratio. The tablets were evaluated for hardness, tensile strength, and drug content, friability and were found satisfactory. The disintegration time in the oral cavity was also tested. The rapidly disintegrating tablets with proper hardness, rapidly disintegrates in the oral cavity with enhanced dissolution, which is achieved by using selected superdisintegrants.

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DEPARTMENT OF PHARMACEUTICS – JKKNATTRAJA COLLEGE OF PHARMACY Page 22 Patel B et al., (2009)³² fast dissolving tablets of glipizide were prepared by direct compression method with a view to enhance patient compliance. Two superdisintegrants viz, crospovidone and croscarmellose sodium (4%, 5%, 6%) with different binders viz, pvp k-30 and pregelatinized starch (3%) were used. The prepared batches of tablets were evaluated for hardness, friability, weight variation, disintegration, wetting time, drug content and in vitro dissolution studies. Based on evaluating parameters, Formulation prepared by using 5%

croscarmellose sodium with 3% PVP K30 was selected as optimized formulation. Finally, the optimized formulation was compared with marketed conventional formulation. Stability studies were carried out at 25ºC / 60% RH and 40ºC / 75% RH for optimized formulation for 2 months. Stability studies on the optimized formulation indicated that there was no significant change found in physical appearance, disintegration time and wetting time of the tablets.

Singh J et al., (2009)³³ formulate and optimize an orodispersible formulation of meloxicam using a 2² factorial design for enhanced bioavailability. The tablets were made by non-aqueous wet granulation using crospovidone and mannitol. A 2² factorial design was used to investigate the amount of crospovidone and taste masking, soothening hydrophilic agent (mannitol), as independent variables, and disintegration time as dependent response.

Formulated orodispersible tablets were evaluated for weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio and in vitro drug release. All the formulations satisfied the limits of orodispersion with a dispersion time of less than 60 sec.

Radke R.S et al., (2009)³⁴ prepare orodispersible tablets of baclofen using various concentrations of superdisintegrant agents like Ac-Di-Sol, crospovidone, sodium starch glycolate by direct compression method. Nine formulations having superdisintegrants at different concentration levels were prepared. These tablets were evaluated for drug content, weight variation, friability, hardness, wetting time and in vitro disintegration time. Among the