Osmotic Drug Delivery System Research Articles

Microstructural investigation to the controlled release kinetics of monolith osmotic pump tablets via synchrotron radiation X-ray microtomography

Tomographic imaging techniques are attractive tools for the visualization of the internal structural characteristics of pharmaceutical solid dosage forms. In this paper, the internal structure of the tablet core for a monolith osmotic drug delivery system, felodipine sustained-release tablet, was visualized via synchrotron radiation X-ray computed microtomography during the drug release process. The surface areas and three dimensional parameters of the tablet core were calculated based on the three dimensional reconstruction of the images. At different stages of the drug release process, the surface morphology, the hydration, the swelling, and the structure changing of the tablet, were visualized from the two dimensional monochrome X-ray images. The three dimensional volumes of the remaining tablet core correlated well with the percentages of felodipine (R=0.9988). Also, the three dimensional surface area almost unchanged during the drug release process, which clearly demonstrated the intrinsic drug release mechanism of the osmotic drug delivery system. In conclusion, the synchrotron radiation X-ray computed microtomography, with rapid acquisition, high intensity and micro-scale spatial resolution, was found to be a useful tool for the quantitative elucidation of the intrinsic drug release kinetics and the three dimensional parameters such as surface areas of the remained core obtained by the synchrotron radiation. Thus, X-ray computed microtomography can be considered as a new and complimentary analytical tool to standard compendial pharmaceutical tests for quality control of osmotic drug delivery systems.

Osmotically Controlled Drug Delivery System with Associated Drugs

Conventional drug delivery systems have slight control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the controlled or modified release drug delivery systems. They include dosage forms for oral and transdermal administration as well as injectable and implantable systems. For most of drugs, oral route remains as the most acceptable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Development of an extended release dosage form also requires reasonable absorption throughout the gastro-intestinal tract (GIT). Among the available techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most appropriate one. Osmotic drug delivery systems release the drug with the zero order kinetics which does not depend on the initial concentration and the physiological factors of GIT. This review brings out new technologies, fabrication and recent clinical research in osmotic drug delivery.

Design and evaluation of osmotic pump-based controlled release system of Ambroxol Hydrochloride

The purpose of the present study was to design and evaluate an osmotic pump-based drug delivery system for controlling the release of Ambroxol Hydrochloride (Amb). Citric acid, lactose and polyethylene glycol 6000 (PEG 6000) were employed as osmotic agents. Surelease EC containing polyethylene glycol 400 (PEG 400) controlling the membrane porosity was used as semi-permeable membrane. The formulation of tablet core was optimized by orthogonal design and evaluated by weighted mark method. The influences of the amount of PEG 400 and membrane thickness on Amb release were investigated. The optimal osmotic pump tablet (OPT) was evaluated in different release media and at different stirring rates. The major release power confirmed was osmotic pressure. The release of Amb from OPT was verified at a rate of approximately zero-order, and cumulative release percentage at 12 h was 92.6%. The relative bioavailability of Amb OPT in rabbits relative to the commercial sustained capsule was 109.6%. Our results showed that Amb OPT could be a practical preparation with a good prospect.

Optimization and Development of Swellable Controlled Porosity Osmotic Pump Tablet for Theophylline

Purpose: To develop swellable controlled porosity osmotic pump tablet of theophylline and to define the formulation and process variables responsible for drug release by applying statistical optimizationtechnique.Methods: Formulations were prepared based on Taguchi Orthogonal Array design and Fraction Factorial design for core and coating, respectively. The tablets were prepared by direct compression and wet granulation methods; spray coated with ethyl cellulose solution containing varying amounts ofPEG 400 and plasdone. Drug release from the osmotic drug delivery system was studied using USP Type I paddle type apparatus. The membrane morphology of the delivery system was determined byscanning electron microscopy (SEM).Results: Optimization results indicated that the release rate of theophylline from the swellable controlled porosity osmotic pump tablet is directly proportional to the levels of osmotic agent, solubilizing agent andpore former in the tablet core and the membrane, respectively. SEM showed the formation of pores in the membrane through which drug release occurred. The best formulation showed 98.2 % drug releaseand complied with USP requirements.Conclusion: The results confirmed that the factors responsible for drug release were osmotic agents (core) and pore former (membrane). Also, the preparation of swellable controlled porosity osmotic pumptablet was facilitated by coating the core tablet with pore forming agent, thus eliminating the need for the more expensive laser drilling.

Floating Osmotic Drug Delivery System of Ranitidine Hydrochloride: Development and Evaluation—A Technical Note

Under certain circumstances prolonging the gastric retention of a delivery system is desirable for achieving greater therapeutic benefit of the drugs. For example, drugs that are absorbed in the proximal part of the gastrointestinal tract (1), and drugs that are less soluble in or are degraded by the alkaline pH may benefit from prolonged gastric retention (2). In addition, for local and sustained drug delivery to the stomach and proximal small intestine to treat certain conditions, prolonged gastric retention of the therapeutic moiety may offer numerous advantages including improved bioavailability and therapeutic efficacy, and also the possible reduction of dose size (3). Gastroretentive drug delivery systems (GRDDS) can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Various GRDDS reported in literatures provide controlled delivery of drugs in matrix and/or reservoir type systems. The release of drugs from reservoir/matrix type systems is affected by hydrodynamic conditions of the absorption site and also results in bioavailability fluctuation due to gastric pH variation. Osmotic drug delivery system (ODDS) utilizes the principles of osmotic pressure for controlled delivery of drugs (4). Drug release from these systems is independent of pH and other physiological parameters to a large extent and exhibit significant in vitro–in vivo correlation (5). Drug delivery from ODDS follows zero-order kinetics hence provides better control over in-vivo performance. Ranitidine hydrochloride (RH) is a histamine H2-receptor antagonist. It is widely prescribed in active duodenal ulcers, gastric ulcers, Zollinger–Ellison syndrome, gastroesophageal reflux disease, and erosive esophagitis (6). The recommended adult oral dosage of ranitidine is 150 mg twice daily or 300 mg once daily. The effective treatment of erosive esophagitis requires administration of 150 mg of ranitidine four times a day (6). A frequent dosage schedule for patients often leads to poor patient compliance; thus a sustained release dosage form of RH is desirable. The short biological half-life of drug (2.5–3 h) also favours for development of a sustained release formulation. A traditional oral sustained release formulation of RH releases most of the drug at the colon; due to less solubility of RH in small intestine, thus the drug have absorption window in the colon or in stomach. Ranitidine is absorbed only in the initial part of the small intestine and has 50% absolute bioavailability (6). Moreover, colonic metabolism of ranitidine is partly responsible for the poor bioavailability of ranitidine from the colon (7). These properties of RH do not favour the traditional approach to sustained release delivery. Hence, clinically acceptable sustained release dosage forms of RH prepared with conventional technology may not be successful. With all these considerations in mind, we designed floating osmotic drug delivery system (FODDS) of RH. FODDS consists of an osmotic core (containing drug, osmotic agent and excipients), an inner semipermeable membrane (SPM), and an outer compression coating of gelling agent containing gas generating agent and an orifice drilled through both membranes for delivery of drug. When system comes in contact with gastric environment, gas generating agent, generate CO2 by reacting with the surrounding fluid, the gas generated is trapped and protected within the gel (formed by hydration of gelling agent), thus decreasing the density of tablet. As the density of tablet falls below 1 (density of water), the tablet becomes buoyant. At the same time, the osmotic core also draws surrounding fluid across semipermeable membrane because of osmotic pressure gradient and form saturated solution of the drug. This pressure is relieved by the flow of saturated solution of drug through the delivery orifice.

An Overview of Recent Patents on Oral Osmotic Drug Delivery Systems

In recent years, novel drug delivery systems (NDDS) have been recognized as an attractive niche for the pharmaceutical and health industry. Among various NDDS, osmotic drug delivery systems (ODDS) are most interesting and widely applicable. Osmotic drug delivery system use osmotic pressure for controlled delivery of active agent(s). Drug delivery from these systems, to a large extent is independent of the physiological factors of gastrointestinal tract. ODDS have matured from their use with laboratory animals to most reliable controlled release systems for humans. Most of the knowledge about ODDS is found in patents, which are difficult to read, analyze and judge because of their peculiar style in which they are written. Santus and Baker reviewed ODDS patents up to year 1993; this review article gives an overview of ODDS patents from year 1994 to 2006.

삼투정을 이용한 약물전달기술 특허의 진화과정

Such osmotic drug delivery systems are based on osmosis, the diffusion of water transversely from a medium with a low osmotic pressure to a medium with a high osmotic pressure for the controlled delivery of active agents. In this review, U.S. Patents on osmotic drug delivery analyze 261 patents until December 2001. These devices form now a major market of drug delivery products. Because of their advantage and innovate idea, it appears that the future of oral drug delivery mark,et in Korea is promising.

Controlled porosity solubility- and resin-modulated osmotic drug delivery systems for release of diltiazem hydrochloride

The drug release kinetics from controlled porosity osmotic pumps have been effectively manipulated through application of either solubility- or resin-modulation methods. The solubility of diltiazem hydrochloride was modulated (reduced) for an extended period of 12–14 h through incorporation of controlled release sodium chloride elements into the core tablet formulations. Other diltiazem hydrochloride core tablets were prepared which contained the positively charged anion-exchange resin (poly(4-vinylpyridine). In both instances, in vitro diltiazem hydrochloride release profiles that were zero-order and pH-independent were obtained without chemical modification of the drug. Release from devices that contained neither solubility- nor resin-modulation components was substantially first-order and highly pH-dependent. Solubility-modulated devices administered to dogs released diltiazem hydrochloride with similar in vivo/in vitro kinetics. These approaches may be applied in general to extend osmotic pump technology to drugs with intrinsic water solubilities that are too high or low for conventional osmotic pump formulations.

Influence of cimetidine on steady state concentration and metabolite formation from antipyrine infused with a rectal osmotic mini pump.

The utility of an osmotic rectal drug delivery system as a tool in steady-state pharmacokinetic interaction studies has been investigated using the cimetidine-antipyrine interaction. Antipyrine was administered to six healthy male volunteers at the rate of 15 mg/h until steady-state was reached. Cimetidine 400 mg was then given followed by 200 mg cimetidine after 2, 4 and 6 h. Antipyrine kinetics in plasma and saliva were assessed, and metabolite excretion was determined in urine. Antipyrine levels in plasma and saliva increased shortly after cimetidine administration, indicating inhibition of antipyrine metabolizing enzymes. From the metabolite data it was concluded that all major metabolic pathways of antipyrine were affected to the same extent. The effect lasted somewhat longer than anticipated on the basis of the plasma cimetidine concentrations, but it had disappeared within 48 hours after cessation of treatment. It is concluded that the osmotic rectal drug delivery system is a useful tool in pharmacokinetic interaction studies, because it provides very constant steady-state concentrations, thus permitting investigation of the time course of drug interactions.

Osmotic delivery systems for the beta-adrenoceptor antagonists metoprolol and oxprenolol: design and evaluation of systems for once-daily administration.

The essential features and mode of action of oral osmotic drug delivery systems (Oros) for metoprolol fumarate and oxprenolol succinate are described. Critical aspects in the development of systems for once-daily administration of both drugs are discussed, and methods for evaluating in vitro release characteristics are presented. In vitro testing confirmed that drug delivery corresponded closely to the theoretical release behaviour predicted from the physicochemical and membrane permeability characteristics for both oxprenolol and metoprolol systems. In vitro release rates were also shown to be unaffected by pH, in vitro test procedures, dissolution media and long-term storage at different temperatures.