Pharmaceutical Technology: Controlled Drug Release, Volume 2

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8 Topical release and permeation studies of propranolol hydrochloride from hydrophilic polymeric matrices C.Pillai, A.Baber and F.M.Plakogiannis Division of Pharmaceutics and Industrial Pharmacy, Arnold & Marie Schwartz College of Pharmacy, Long Island University, Brooklyn, NY 11201, USA SUMMARY In vitro release of propranolol hydrochloride, a commonly used β-adrenergic blocking agent, form various hydrophilic polymeric gels was studied. These included: Methocel ® , Avicel ® , polyvinyl alcohol, methyl cellulose and gelatin-based systems. Several ingredients, such as ethyl alcohol, dimethylsulphoxide (DMSO) and polyethylene glycol 400 were included in the formulations at various concentration levels for possible enhancement of drug release. The release studies were carried out using a cellulose membrane and hairless mouse skin as the diffusion barriers. The general rank order for the drug release through these membranes was observed to be as follows: Methocel ® matrix>Avicel ® CL-611 matrix>PVA-gelatin matrix>emulsion base. The inclusion of other ingredients in the formulations had little or no effect in enhancing the drug release. However, when the hairless mouse skin was soaked in DMSO for 1 h prior to use in the diffusion studies, the drug release was increased by 40%. The amount of propranolol hydrochloride released from the Methocel ® matrix in 24 h was observed to be well within the therapeutic range, i.e. 0.21– 0.81 mg per litre. The in vitro release data were treated with various kinetic models to assess the diffusion coefficient, the partition coefficient and the permeability coefficient. Using this information, the formulations evaluation were screened from their suitability to deliver propanolol hydrochloride as a topical dosage form.
90 CH. 8] TOPICAL RELEASE AND PERMEATION STUDIES INTRODUCTION Propranolol, an effective β-adrenergic blocking agent, was first introduced on the market as Inderal ® by Ayerst laboratories, Inc. [1,2]. It was approved by the Food and <strong>Drug</strong> Administration initially for the treatment of cardiac arrhythmias in 1968, then for the treatment of angina pectoris in 1973 and finally as an antihypertensive agent in 1976. In addition to its effectiveness in the management of hypertension [3–8], it has been found to be useful in the treatment of hyperthyroidism [9]. Lately it has been indicated in the prophylaxis of migraine headache. Propranolol is chemically a naphthol derivative (dl-(isopropylamino)-3-(l-naphthyloxy)-2- propanol). It is a racemic mixture, and the laevo form is the active β-adrenergic blocking agent [10]. After oral administration, it is completely absorbed [11]. However, the systemic availability is relatively low with considerable variation in plasma levels [12,13]. The hepatic extraction of propranolol is about 80– 90%, and thus the main route of drug elimination is via hepatic metabolism [14]. One of the major metabolites of propranolol is 4-hydroxypropranolol, and the halflife has been reported to be 3±1−1/2h [15–18]. Since the drug is rapidly metabolized after oral administration, it necessitates a multiple dosage after oral strict patient compliance. The therapeutically effective concentration of propranolol has been established to be 0.21–0.81 mg per litre and the lethal concentration in the range 8–12 mg per litre [19]. Some of untoward effects of propranolol therapy are associated with the gastrointestinal tract, i.e. nausea, vomiting, mild diarrhoea and constipation, etc. The drug also affects the central nervous system causing lassitude, asthenia, visual disturbances and rarely hallucination. It may sometimes produce erythmatous rash with fever, sore throat, orthostatic hypotension, hypoglycaemia and bronchospasm. At present, the pharmaceutical industry has invested a major slice of its research and development efforts in the development of novel drug delivery dosage forms. Generally, this is to maximize the drug efficacy and to minimize the side effects usually associated with the conventional oral route of drug administration. In addition to the popular controlled release dosage forms, the transdermal route of drug delivery is being extensively investigated. Consequently, several transdermal patches of clinically important drugs, such as scopolamine and transglycerin, have been successfully marketed. These types of transdermal drug delivery systems are designed to deliver the medication gradually into the body in a preprogrammed fashion. These dosage forms present the drug to the patient in a most convenient and acceptable manner [20]. In the light of these observations and the newer trends in product formulation, it was decided to study the in vitro release and permeation of propranolol hydrochloride from various hydrophilic polymeric matrices using the cellulose membrane and the hairless mouse skin as the diffusion barriers and to evaluate the effects of some of the additive ingredients known to enhance drug release from dermatological bases.
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PHARMACEUTICAL TECHNOLOGY Controlle
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First published in 1991 by ELLIS HO
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CH. 1] INFLUENCE OF DRUG SOLUBILITY
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162 CH. 15] A SUSTAINED RELEASE OPH
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194 INDEX dry granulation, 43 elect
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Pharmaceutical Technology: Controlled Drug Release, Volume 2

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