FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLETS FROM SOLID DISPERSIONS OF LOVASTATIN

About Authors:
Khayyam Shaikh*, Patwekar Shailesh, Santosh Payghan, John Disouza
Department of Pharmaceutics,
Tatyasaheb Kore College of Pharmacy,
Warananagar, Kolhapur, Maharashtra, India 416113.
*ramzanshek0587@gmail.com

ABSTRACT
During the last two decades there has been a remarkable increase in interest in sustained release drug delivery system. This has been due to various factors viz. the extensive cost of developing new drug entities, expiration of existing international patents, discovery of new polymeric materials suitable for prolonging the drug release, and improvement in therapeutic efficacy and safety achieved by this delivery system. A number of design options are available for the preparation of controlled release formulations to modify oral absorption. Formulation approaches are being explored to enhance bioavailability of poorly water-soluble drugs. One such approach that has been shown significantly enhanced absorption of such drugs is to formulate solid dispersionand then formulate its tablets. Solid dispersion technology can be used to improve the in- vitro and in- vivo dissolution properties of slightly water soluble drugs and to control their dissolution rate. In this current study attempts have been made to formulate sustained release tablets of solid dispersions.


Reference Id: PHARMATUTOR-ART-1612

INTRODUCTION
The term sustained release has been constantly used to describe a pharmaceutical dosage form formulated to retard the release of a therapeutic agent1.

The term controlled release on the other hand has a meaning that goes beyond the scope of sustained drug action. It also implies predictability and reproducibility in the drug release kinetics, which means that the release of drug ingredients from a controlled release drug delivery system proceeds at a rate profile that is not only predictable kinetically, but also reproducible from one unit to other2.

During the last two decades there has been a remarkable increase in interest in sustained release drug delivery system. This has been due to various factors viz. the extensive cost of developing new drug entities, expiration of existing international patents, discovery of new polymeric materials suitable for prolonging the drug release, and improvement in therapeutic efficacy and safety achieved by these delivery system3. Now-a-days the technology of sustained release has also being applied to veterinary products4.


Figure 1: Drug level versus time.


Advantages of sustained release dosage form5,6,7 : Various advantages of sustained release dosage forms include increased patient compliance due to reduced frequency of drug administration, reduced night time dosing, reduced patient care time, constant supply of drug is provided, decreased local and systemic side effects, reduced gastrointestinal irritation, better drug utilization, reduction in total amount of drug used etc.

Development of controlled release drug delivery systems provide a uniform concentration or amount of drug at absorption site, maintained plasma concentration within a therapeutic range, minimizes the side effects and reduces the frequency of drug administration8. In the last decade, a considerable attention has been focused on the development of novel drug delivery systems because of their obvious advantages such as ease of administration, controlled releases of drug at slower predetermined rate, effectiveness in the treatment at chronic conditions and better patient convenience due to simplified dosing schedule. A number of design options are available for the preparation of controlled release formulations to modify oral absorption. Formulation approaches are being explored to enhance bioavailability of poorly water-soluble drugs. One such approach that has been shown significantly enhanced absorption of such drugs is to formulate solid dispersion9and then formulate its tablets.

Solid dispersion technology: Solid dispersion technology can be used to improve the in- vitro and in- vivo dissolution properties of slightly water soluble drugs and to control their dissolution rate10.Solid dispersion is a product formed by converting a fluid drug carrier combination into solid state11.

Methods of preparation of solid dispersion 11,12: Two methods were used to prepare solid dispersions viz. Melting (fusion) method and Solvent method.

Stability problems of solid dispersions 13: The solid dispersion technique is used for increasing dissolution and absorption rate of poorly soluble drugs. Although the use of solid dispersions has been reported frequently in pharmaceutical literature, very few marketed products rely on solid dispersion strategy. The main reason for this discrepancy is the physical instability (aging effects) of these structures, which are often metastable. Phase separation, crystal growth, or conversion from the amorphous form (metastable form) to crystalline state during storage inevitably results in decreased solubility and dissolution rate.

The proper selection of carrier is often adequate to prevent instability. A carrier that will increase the glass transition temperature (Tg) of the binary system so that molecular mobility becomes extremely low at room temperature, thereby leading to acceptable physical stability. Thus such solid dispersions can be used to formulate sustained release tablets.

Stabilization of lovastatin14: HMG-CoA reeducates inhibitors, stability in an acidic environment is one of a major problems. In order to achieve suitable dosage forms comprising HMG-CoA reductase inhibitors, it is desirable to adequately protect the active ingredient against pH-related destabilization. Stabilization of lovastatin can be achieved by enteric coating of tablets.

Objectives: Lovastatin is a hypolipedimic agent and is insoluble in water as a result, its oral bioavailability is just less than 5% .This necessitates the administration of unnecessarily larger dose of drug. In addition to this the drug has a half-life of 1.1-1.7 hours which requires frequent administration of drug. Thus attempts have been made to formulate solid dispersions and its sustained release tablets with following objectives.

1. To improve solubility and dissolution characteristics of Lovastatin, in order to enhance its oral bioavailability by developing solid dispersions using water soluble carriers.
2. To reduce dose, dosing frequency and dose related side effects by developing sustained release tablets in order to improve patient compliance.
3. To improve the stability of lovastatin in stomach by enteric coating of the tablets.

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