Chugh Isha et al. IRJP 2012, 3 (5) INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 – 8407 Review Article ORAL SUSTAINED RELEASE DRUG DELIVERY SYSTEM: AN OVERVIEW Chugh Isha1*, Seth Nimrata1, Rana A.C.2, Gupta Surbhi1 1Rayat Institute of Pharmacy, Department of Pharmaceutics, Ropar , S.B.S Nagar-144533 (Punjab) India 2Rayat Institute of Pharmacy, Department of Pharmacology, Ropar, S.B.S Nagar- 144533 (Punjab) India Article Received on: 19/04/12 Revised on: 30/04/12 Approved for publication: 20/05/12 *E mail: [email protected] ABSTRACT In the recent years, focus on the development of oral controlled release drug delivery systems has increased. Oral ingestion has been the most convenient and commonly employed route of drug delivery. Indeed, for sustained-release systems, the oral route of administration has by far received the most attention with respect to research on physiological and drug constraints. Sustained release dosage forms are designed to release a drug at a predetermined rate by maintaining a constant drug level for a specific period of time with minimum side effects. Sustained release of drugs in gastrointestinal tract following oral administration is not affected by the absorption process. Here this article concentrates on preparations, factors influencing, design, formulation, and the evaluation of oral sustained release preparations. The principal goal of sustained release dosage forms is the improvement of drug therapy assessed by the relationship between advantages and disadvantages of the use of sustained release systems. Key words: Controlled drug delivery system, Sustained release preparations, Factors influencing, Oral route of administration, Pre-determined rate INTRODUCTION various disciplines, including GI physiology, If one were to imagine the ideal drug delivery system, two pharmacokinetics, pharmacodynamics and formulation prerequisites would be required. First, it would be a single design are essential to achieve a systemic approach to the dose for the duration of treatment, whether it be for days or successful development of an oral pharmaceutical dosage weeks, as with infection, or for the lifetime of the patient, as form. The more sophisticated a delivery system, the greater is in hypertension or diabetes. Second, it should deliver the the complexity of these various disciplines involved in the active entity directly to the site of action, thereby minimizing design and optimization of the system. In any case, the or eliminating side effects. This may necessitate delivery to scientific framework required for the successful development specific receptors, or to localization to cells or to specific of an oral drug delivery system consists of a basic areas of the body.In the past decade great interest got understanding of the following three aspects: generated on replacing conventional administration of drugs 1. Physicochemical, pharmacokinetic and pharmacodynamic by novel delivery systems which would release effective characteristics of the drug. quantities from a protected supply at a controlled rate over a 2. The anatomic and the physiologic characteristics of the long period of time. Ideally a drug to provide desired GIT. therapeutic action should arrive rapidly at the site of action 3. Physicochemical characteristics and drug delivery mode of (receptor) in optimum concentration, remain there for desired the dosage form to be designed. time, spare other sites and get removed from the site. One of The goal in designing sustained or controlled delivery the interesting results of pharmaceutical research is the fact system is to4,5 that absorption rate of a drug can be decreased by reducing its Over the past 30 years, as the expense and complications rate of release from the dosage form. The products so involved in marketing new drug entities have increased, with formulated are designated as sustained action, sustained concomitant recognition of the therapeutic advantages of release, delayed action, prolonged action, depot, repository, novel drug delivery, greater attention has been focused on retarded release and timed release medication1,2. development of sustained or controlled release drug delivery ORAL ROUTE AS THE MOST CONVENIENT system. There are several reasons for the attractiveness of ROUTE3,4,5 these dosage forms. It is generally recognized that for many Oral ingestion has been the most convenient and commonly disease states, a substantial number of therapeutically employed route of drug delivery. Indeed, for sustained- effective compounds already exists. The effectiveness of release systems, the oral route of administration has by far these drugs however is often limited by side effects or the received the most attention with respect to research on necessity to administer the compound in a clinical setting. physiological and drug constraints as well as design and The major goal set in designing sustained or controlled testing of products. This is because there is more flexibility in delivery is to: dosage form design for the oral route than there is for the · Reduce the frequency of dosing. parenteral route.The reason that the oral route achieved such · Increase effectiveness of the drug by localization at popularity may be in part attributed to its ease of the site of action. administration as well as the traditional belief that by oral · Reducing the dose required. administration the drug is well absorbed as the food stuffs · Providing the uniform drug delivery. that are ingested daily. In fact, the development of In the past, many of the terms used to refer therapeutic pharmaceutical product for oral delivery, irrespective of its systems of controlled and sustained release have been used in physical form involves varying extent of optimization of an inconsistent and confusing manner. Sustained release, dosage form characteristics within the inherent constraints of sustained action, prolonged action, controlled release (drug GI physiology. Therefore the fundamental understanding of release with zero order kinetics) and repository dosage forms Page 57 Chugh Isha et al. IRJP 2012, 3 (5) are terms used to identify drug delivery systems that are Disadvantages8 designed to achieve prolonged therapeutic effects by 1. Dose dumping: continuously releasing medication over an extended period of · Dose dumping may occur with faulty formulations. time after administration of a single dose. 2. Need for additional patient education: MODIFIED-RELEASE DELIVERY SYSTEMS MAY · Patients may need substantial additional information as to BE DIVIDED CONVENIENTLY IN TO FOUR the proper use of sustained release products e.g. “Do not CATAGORIES6 crush or chew the dosage unit. Tablet residue may appear · Delayed release. in the stools”. In some instances, patients must be started · Sustained release. on an immediate release product and then switched over · Site-specific targeting. to the sustained release products. · Receptor targeting. 3. Possible reduction in systemic availability: Sustained-release systems include any drug-delivery system · Reduced systemic availability has been shown for some that achieves slow release of drug over an extended period of sustained release formulations of Theophylline, time. If the systems can provide some control, whether this is Procainamide and Vitamin combinations. of a temporal or spatial nature, or both, of drug release in the BIOLOGICAL FACTORS INFLUENCING ORAL body, or in other words; the system is successful at SUSTAINED-RELEASE DOSAGE FORM DESIGN1 maintaining constant drug levels in the target tissue or cells, it 1. Biological Half-life is considered a controlled-release system. Drug molecules with short half-life are excellent candidate Sustained Release Preparation7 for sustained-release formulation, since this can reduce These preparations may provide an immediate dose required dosing frequency. However, this is limited, in that drugs with for the normal therapeutic response, followed by the gradual very short half-lives may require excessive large amounts of release of drug in amounts sufficient to maintain the drug in each dosage unit to maintain sustained effects, therapeutic response for a specific extended period of time forcing the dosage form itself to become limitingly large. In usually 8-12 hrs. The major advantage of this category is that, general drugs with half-lives shorter than 2 hr such as in addition to the convenience of reduced frequency of furosemide or levodopa are poor candidates for sustained- administration, it provides blood levels that are devoid of the release preparations. peak and valley effect which are characteristics of the 2. Absorption conventional intermittent dosage regimen. Sustained release The absorption rate constant is an apparent rate constant, and dosage forms are designed to complement the pharmaceutical should, in actuality, be the release rate constant of the drug activity of the medicament in order to achieve better from the dosage form. Compounds that demonstrate the selectivity and longer duration of action. absorption rate constant will probably be poor candidates for Controlled Release Preparations8 sustaining systems. If a drug is absorbed by active transport, Although this term has been interchanged widely with or transport is limited to a specific region of intestine, sustained release preparation in the past, recently it has sustained-release preparations may be disadvantageous to become customary to restrict the latter term to formulations absorption. where the mechanism of prolonged