RESUMO
We reported the physical chemical characterization of a new series of native dextran (B110-1-2). The chemical structure of the polymer was characterized by IR, (1)H and (13)C NMR spectroscopy and compared with that of a commercial native dextran B512-F obtained from Sigma Company. Molecular weights of the product and different commercial dextran fractions of Leuconostoc mesenteroides from 43000 to 170000 average molecular weight (M(w)) were established by the analysis of intrinsic viscosity in aqueous solutions and compared with those obtained by gel permeation chromatography (GPC). The critical overlap concentration around 9g/L was obtained. No interactions of powder mixtures with different commercial excipients (lactose, cetyl alcohol, HPMC) and drugs (propranolol hydrochloride, acetyl salicyclic acid, isosorbide dinitrate, lobenzarit disodium, and nifedipine) were demonstrated by differential scanning calorimetry (DSC) analysis. Tablets obtained by direct compression showed good physical-mechanical and technological properties. Dextran B110-1-2 has similar physical chemical properties as commercial Sigma B512-F. Water uptake, erosion and dissolution profile studies for dextran tablets established that glucose polymer with molecular weight M(w) > or = 2x10(6) is suitable for the development of controlled release solid dosage forms (soluble drugs). Fraction of dextran (M(w) 40000-170000) could be more useful for immediate release tablets.
Assuntos
Dextranos/administração & dosagem , Excipientes , Preparações Farmacêuticas , Saccharum/química , Comprimidos , Espectroscopia de Ressonância Magnética , Espectrofotometria Infravermelho , ViscosidadeRESUMO
The objective of the present work is to estimate for the first time the percolation threshold of a new series of dextran (native dextran of high molecular weight [B110-1-2, Mw = 2 x 10(6)]), in matrices of lobenzarit disodium (LBD) and to apply the obtained result to the design of hydrophilic matrices for the controlled delivery of this drug. The formulations studied were prepared with different amounts of excipient in the range of 20% to 70% wt/wt. Dissolution studies were performed using the paddle method (100 rpm) and one face water uptake measurements were performed using a modified Enslin apparatus. The Higuchi, zero-order, and Hixson-Crowell models as well as the nonlinear regression model were employed as empiric methods to study the release data. Values of diffusion exponent 0.563 < n < 0.786 (Korsmeyer equation) for dissolution profile and water uptake mechanism 0.715 < n < 1 (Davidson and Peppas equation) suggested anomalous or complex mechanisms. On the other hand, the contribution of the relaxation or erosion and of the diffusive mechanism in Peppas-Sahlin equation indicated that the main mechanism for drug delivery from tablets is swelling controlled delivery (K(r)/K(d) < 1). The critical points observed in kinetic parameters above 58.63% vol/vol of native dextran B110-1-2 plus initial porosity in the LBD-dextran matrices with a relative polymer/drug particle size of 4.17 were attributed to the existence of an excipient percolation threshold.
Assuntos
Antirreumáticos/química , Dextranos/química , Excipientes/química , ortoaminobenzoatos/química , Química Farmacêutica , Preparações de Ação Retardada , Difusão , Composição de Medicamentos , Cinética , Modelos Químicos , Modelos Estatísticos , Peso Molecular , Tamanho da Partícula , Porosidade , Projetos de Pesquisa , Solubilidade , Comprimidos , Tecnologia Farmacêutica/métodos , Água/químicaRESUMO
A novel oral controlled delivery system for propranolol hydrochloride (PPL) was developed and optimized. The in vitro dissolution profiles of sustained-release matrix tablets of racemic PPL were determined and compared with the United States Pharmacopeia (USP) tolerance specifications for Propranolol Hydrochloride Extended-Release Capsules. The influence of matrix forming agents (native dextran, hydroxypropyl methylcellulose (HPMC), cetyl alcohol) and binary mixtures of them on PPL release in vitro was investigated. A central composite design was applied to the optimization of a sustained-release tablet formulation. The sustained-release matrix tablets with good physical, mechanical and technological properties were obtained with a matrix excipient:PPL ratio of 60:40 (w/w), with a dextran:HPMC ratio of 4:1 (w/w) and with a cetyl alcohol amount of 15% (w/w). A comparative kinetic study of the present matrix tablets and commercial SUMIAL RETARD capsules (Spain) was established. The value for the similarity factor (f(2)=69.6) suggested that the dissolution profile of the present two sustained-release oral dosage forms are similar. Higuchi (diffusion) and Hixon-Crowell (erosion) kinetic profiles were achieved and this codependent mechanism of drug release was established.