Dissolution Rate Enhancement of Nifedipine and Development of Controlled Release Matrix Tablets of Nifedipine Dispersions

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STUDIES ON DISSOLUTION RATE ENHANCEMENT OF NIFEDIPINE AND DEVELOPMENT OF CONTROLLED RELEASE MATRIX TABLETS OF NIFEDIPINE DISPERSIONSDissertation submitted to The Acharya Nagarjuna University, Nagarjuna Nagar, In partial fulfillment for the award of degree of

BACHELOR OF PHARMACYBy

PRATHYUSHA. G

(Y5PH935)

Under the Guidance of Dr. S. Vidyadhara, M. Pharm., Ph.D., Professor and Principal.

APRIL 2009

CHEBROLU HANUMAIAH INSTITUTE OF PHARMACEUTICAL SCIENCES GUNTUR- 19

CERTIFICATE

This is the bonafide dissertation work on studies on Dissolution Rate Enhancement of Nifedipine and Development of Controlled Release Matrix Tablets of Nifedipine Dispersions by Leena. A, Pavanaraghava. G, Prathyusha. G and Sireesha. K The work mentioned in this dissertation was carried out at Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, under the supervision of Dr. S. Vidyadhara, M.Pharm.,Ph.D., Professor and Principal.

Dr. S. Vidyadhara, M.Pharm.,Ph.D., Professor and Principal, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur- 19.

CERTIFICATE

This is the bonafide dissertation work on studies on Dissolution Rate Enhancement of Nifedipine and Development of Controlled Release Matrix Tablets of Nifedipine Dispersions has been carried out by Leena. A, Pavanaraghava. G, Prathyusha. G and Sireesha. K in Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, under my guidance and supervision.

Dr. S. Vidyadhara, M.Pharm.,Ph.D., Professor and Principal, Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur- 19.

DECLARATION

We here by declare that the work incorporated in this dissertation has been carried out at Chebrolu Hanumaiah Institute of Pharmaceutical Sciences, Guntur, A.P, India. The work is original and has not been submitted in part or full for any other diploma or degree of this or any other university.

Place: Guntur Date:

Leena. A PavanaRaghava. G Prathyusha. G Sireesha. K

(Y5PH922) (Y5PH932) (Y5PH935) (Y5PH944)

Acknowledgement It is our pleasant duty to express my deep sense of gratitude and indebtedness to my beloved research guide Mr. R. L. C. Sasidhar, M. Pharm., Lecturer, Chebrolu Hanumaiah Institutte of Pharmaceutical sciences, who have suggested and guided all through the work but also kept my spirit high up with their valuable suggestions and constant encouragement. We express my sincere thanks and gratitude to our Principal Dr. S. Vidyadhara for providing all the resources to complete this work successfully. We are thankful to Dr. k. Basavapunnaiah, President, CHIPS, Dr.M. GopalKrishna, Secretary and Correspondent, CHIPS, Sri. CH. Narendranath, Vice president, CHIPS and other members of Nagarjuna Educational Society, Guntur, for their encouragement in research work. We are greatly indebted to Sri. J. Ramesh Babu, Sri. R. Rambabu, Sri. A. Ramu, Sri. S. Siva Prasad and all other staff members for giving their valuable suggestions for successful completion of my project work. It is our pleasure to express my warm regards and wishes to my friends M. Nagasree, Navya.k and P. Chandana for their help and co-operation during my work. We express our special thanks to Mr. P. Kishore, Mrs. CH. Uma Devi and other non teaching staff for their help during my work. We conclude my acknowledgement by regarding my deep sense of affection to my beloved family for their encouragement and cheerful company throughout this endeavor, without which this work would not have been completed in stipulated period.

Leena. A PavanaRaghava. G Prathyusha. G Sireesha. K

(Y5PH922) (Y5PH932) (Y5PH935) (Y5PH944)

DEDICATED TO MY FAMILY

CONTENTSPg No:

CHAPTER 1: Introduction CHAPTER 2: Literature Review

CHAPTER 3: Materials and Methods CHAPTER 4: Experimental Results CHAPTER 5: Discussion of Results CHAPTER 6: Summary and Conclusions CHAPTER 7: References

CHAPTER I INTRODUCTION

INTRODUCTIONThe bioavailability of most of the drugs depends on dissolution rate and these inturn depend on particle size1. The rate of absorption depends on concentration gradient which is done by increasing dissolution rate and is seen in drugs with limited solubility. The particle size plays an important role in parentral therapy decrease in particle size and leads to delayed absorption. In semisolids improved dissolution rate leads to greater bioavailability and absorbed in to the systemic circulation, The size of droplets governs the deposition of respiratory track in inhalation therapy. Particle size reduction is achieved by 1. Conventional trituration and grinding. 2. Ball milling. 3. Fluid energy micronization. 4. Controlled precipitation by change of liquid solvents or temperature. 5. Administration of liquid solutions from which, up on dilution with gastric fluids, the dissolved drug may precipitate in very fine particles. 6. Administration of water soluble salts of poorly soluble compounds from which the parent neutral forms may precipitate in ultramarine form in GI fluids. Theoritically, the solvent method seems to be an ideal approach to achieve particle size reduction. How ever it is not frequently employed in the commercial market due to such reasons as selection of noin toxic solvets, limitation of drugs with loow dose and the high cost of production. A unique approach of solid dispersion is to reduce the particle size and to increase the rate of dissolution and absorption was first demonstrated in 1961. In addition to absorption enhancement the solid dispersion technique has numerous othe pharmaceutical applications such as homogenous distribution of a small amount of drugs at solid state, to stabilize unstable drugs, to dispense liquid or gaseous compounds, to formulate a fast releasing promising dose in a sustained release regimen of soluble drugs by using a poorly soluble or insoluble carriers.23.

Absorption of drugs

appears to increase with increase in surface area. The viscosity of suspensions increase with

DEFINITION: It is a science of dispersing one or more active ingredients in an inert matrix using in the solid state in order to achieve increased dissolution rate, sustained release of drugs, altered solid state properties and enhances release of drugs from ointment and suppository bases and improves solubility and stability. TYPES OF SOLID DISPERSIONS:

Simple eutectic mixtures: An eutectic mixture of a sparingly water soluble drug and ahighly water soluble carrier may be regarded thermodynamically as an intimately blended physical mixture of its two crystalline components. The increasing surface area is responsible for increased rate of dissolution.

Solid solutions: The solid solution consists of a solid solute dissolved in a solid solvent. Amixed crystal is formed because the two components crystallise together in a homogenous one phase system. Hence this system would expect to yield much higher rate of dissolution than simple eutectic systems.

Glass solutions of suspensions: It is a homogenous system in which a glassy or avitreous of the carrier solubilises drug molecules in its matrix. PVP dissolved in organic solvents undergoes a transition to a glassy state up on evaporation of the solvent .

Compound or complex formation: This system is characterised by complexation oftwo components in a binary system during solid dispersion preparation. The availability of the drug from the complex depends up on the solubility, dissociation constant and intrinsic absorption rate of the complex.

Amorphous precipitation: It occurs when the drug precipitates as an amorphous formin the inert carrier. The high energy state of the drugs in this system generally produces much greater dissolution rates than the corresponding crystalline forms of the drugs.

INTRODUCTION TO CONTROLLED RELEASE DRUG DELIVERY SYSTEMSDuring the past 30 years as the expenses and complications involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of controlled drug delivery, greater attention has been focused on the development of controlled-release drug delivery systems (CRDDS). There are several reasons for the attractiveness of these dosage forms. It is generally recognized that for many disease states, a substantial number of therapeutically effective compounds already exist. The effectiveness of these drugs, however, is often limited by side effects or the necessity to administer the compound in a clinical setting. The goal in designing controlled release systems is to reduce the frequency of dosing or to increase effectiveness of the drug by localization at the site of action, reducing the dose required or providing uniform drug delivery. An Ideal drug delivery system must have two prerequisites 1) It would be a single dose for the duration of treatment, whether it be for days or weeks as with infection or for the lifetime of the patient as in hypertension or diabetes. 2) It should deliver the active entity directly to the site of action, thereby minimizing or eliminating side effects. This may necessitate delivery to specific receptors or to localization to cells or to specific areas of the body. Thus the controlled delivery attempts to deliver the therapeutic agent to a specific site, for a specific time. In other words, the objective is to achieve both spatial and temporal placement of drug. Currently, it is possible to only partially achieve both of these goals, with most drug delivery systems.

Advantages and disadvantages of controlled release systemsAdvantages: 1. Decreased incidence and/or intensity of adverse effects and toxicity 2. Better drug utilization. 3. Controlled rate of release 4. More uniform blood concentrations. 5. Improved patient compliance. 6. Reduced dosing frequency. 7. More consistent and pro

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