Polymer erosion and drug release characterization of hydroxypropyl methylcellulose matrices. 1998

T D Reynolds, and S H Gehrke, and A S Hussain, and L S Shenouda
College of Pharmacy, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0004, USA.

Polymer erosion of matrices of similarly substituted hydroxypropyl methylcellulose (HPMC) polymers was examined, and drug release in terms of diffusion and erosion contributions was characterized, focusing on matrices containing either polymer alone or a drug content of 25% level with no added excipients. A novel approach was utilized to separate diffusional and erosional contributions to drug release. Diffusional drug release was determined by fitting release data versus (time)0.45, and the drug release due to erosion was quantified by subtracting the percent predicted for diffusional drug release from the total drug release at each specific time point. Drug release resulting from polymer erosion was linear versus time and was found to be a function of the number average molecular weight of the polymer. In contrast, diffusional release rates were comparable for all HPMC grades studied and, thus, were independent of number average molecular weight of the polymers studied. Under stirring conditions of 10-100 rpm as well as static condition, the detachment of individual polymer chains at the matrix surface occurred at a faster rate relative to diffusion away from the matrix surface. The erosion study indicated that polymer diffusion of the HPMC polymer chains through the aqueous diffusion layer was the rate-limiting step for polymer erosion. In general, polymer erosion was found to be inversely related to the polymer number average molecular weight. A scaling law was used to relate polymer erosion rate with the respective polymer number average molecular weight. Similar relationships were obtained for matrices with and without drug at a stirring rate of 100 rpm.

UI MeSH Term Description Entries
D008747 Methylcellulose Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. BFL,Celevac,Cellothyl,Cellulone,Citrucel,Cologel,Dacryolarmes,Methocel,Methyl Cellulose,Muciplasma,Cellulose, Methyl
D011433 Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D013607 Tablets Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed) Tablet
D013806 Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP. 1,3-Dimethylxanthine,3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione,Accurbron,Aerobin,Aerolate,Afonilum Retard,Aquaphyllin,Armophylline,Bronchoparat,Bronkodyl,Constant-T,Elixophyllin,Euphylong,Glycine Theophyllinate,Lodrane,Monospan,Nuelin,Nuelin S.A.,Quibron T-SR,Slo-Phyllin,Somophyllin-T,Sustaire,Synophylate,Theo Von Ct,Theo-24,Theo-Dur,Theobid,Theocin,Theoconfin Continuous,Theodur,Theolair,Theolix,Theon,Theonite,Theopek,Theophylline Anhydrous,Theophylline Sodium Glycinate,Theospan,Theostat,Theovent,Uniphyl,Uniphyllin,Uniphylline,1,3 Dimethylxanthine,Anhydrous, Theophylline,Constant T,ConstantT,Ct, Theo Von,Glycinate, Theophylline Sodium,Quibron T SR,Quibron TSR,Slo Phyllin,SloPhyllin,Sodium Glycinate, Theophylline,Somophyllin T,SomophyllinT,Theo 24,Theo Dur,Theo24,Theophyllinate, Glycine,Von Ct, Theo
D065347 Hypromellose Derivatives Polymeric compounds that contain repeating units of hydroxypropyl methylcellulose. The properties of hypromellose polymers can vary greatly and are defined by their molecular weight, the percentage of hydroxyl groups, the percentage of hydroxypropyl groups, and viscosity measurements. They are found a broad variety of commercial products such as FOOD ADDITIVES; EXCIPIENTS; and LUBRICANTS. HPMC 2910,HPMC-K-100 M,Hydroxypropyl Methylcellulose,Hydroxypropylmethylcellulose,Hypromellose,K-8515,K8515,MHPC Polymer,Methocel E,Methoxyhydroxypropylcellulose,Methyl Hydroxypropyl Cellulose,Methyl-hydroxypropyl-cellulose,Derivative, Hypromellose,Derivatives, Hypromellose,HPMC K 100 M,HPMCK100 M,Hypromellose Derivative,K 8515

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