Formulation and Evaluation of Gastroretentive Drug Delivery System of Propranolol Hydrochloride

Abstract

Abstract. The objective of present study was to develop a gastroretentive drug delivery system of propranolol hydrochloride. The biggest problem in oral drug delivery is low and erratic drug bioavailability. The ability of various polymers to retain the drug when used in different concentrations was investigated. Hydroxypropyl methylcellulose (HPMC) K4 M, HPMC E 15 LV, hydroxypropyl cellulose (HPC; Klucel HF), xanthan gum, and sodium alginate (Keltose) were evaluated for their gelforming abilities. One of the disadvantages in using propranolol is extensive first pass metabolism of drug and only 25% reaches systemic circulation. The bioavailability of propranolol increases in presence of food. Also, the absorption of various drugs such as propranolol through P-glycoprotein (P-gp) efflux transporter is low and erratic. The density of P-gp increases toward the distal part of the gastrointestinal tract (GIT). Therefore, it was decided to formulate floating tablet of propranolol so that it remains in the upper part of GIT for longer time. They were evaluated for physical properties, in vitro release as well as in vivo behavior. In preliminary trials, tablets formulated with HPC, sodium alginate, and HPMC E 15 LV failed to produce matrix of required strength, whereas formulation containing xanthan gum showed good drug retaining abilities but floating abilities were found to be poor. Finally, floating tablets were formulated with HPMC K4 M and HPC.

Development of Controlled-Release Matrix Tablet of Risperidone: Influence of Methocel®- and Ethocel®-Based Novel Polymeric Blend on In Vitro Drug Release and Bioavailability

“…Hydroxypropyl methylcellulose (HPMC, hydrophilic) has been a popular release-retarding polymer in simple matrix tablets (19,20) and floating gastro-retentive tablets (21,22). Fine particle ethyl cellulose (FPEC) was successfully used in the formulation of extended-release tablets of some non-ionizable drugs (23).…”

Formulation of Metformin HCl Floating Tablet using HPC, HPMC K100M, and the Combinations

“…The main requirement for preparation can float is the system must continue to have a specific gravity lower than the overall specific gravity of the specific contents of the stomach [11]. When the density of tablets was less than 1, the tablet becomes floating [7]. Differences floating lag time can be influenced by the molecular weight of each polymer.…”

“…HPC is easily soluble in water temperatures below 38 °C, in hot water, insoluble and precipitates form a precipitate which expands at a temperature between 40-45 °C. HPC probably could not resist the drug release in dissolution conditions used [7]. The polymers used in the formulation of a floating tablet dosage form should be able to form a barrier gel that is cohesive and should dissolve slowly, as an appropriate drug reservoir [13].…”

“…As a result, the floating tablet formulated using HMPC K4M gave the best detention effect of release of the drug about 92% for 18 hours, in which tablets formulated with HPMC E15LV, HPC, and carbopol could not form a matrix. Tablets formulated with xanthan gum show the ability to withstand drug release, but have poor floating capabilities [7]. In addition, Sungthongjeen, et al [8] has formulated a theophylline floating tablet with several HPMC types, HPMC K100LV, HPMC K4M, and HPMC K100M by the method of wet granulation, in which tablets formulated with HPMC K100M demonstrated the ability to withstand the best release of drugs.…”

Technologies, Optimization and Analytical Parameters in Gastroretentive Drug Delivery Systems

“…Peak plasma concentration of propanolol is reached after 1-4 h via oral route and its t1/2 is 3-4 h. In consequence with first-pass metabolism, all these attributes increase its ability to be delivered via a controlled release system. Consequently, GRDDS can increase oral bioavailability of propanolol by reducing its high first-pass metabolism 33,34 . Excipients are more likely selected according requirement of the drug delivery systems.…”