Effect of added Pharmatose DCL11 on the sustained-release of metronidazole from Methocel K4M and Carbopol 971P NF floating matrices.

In vitro dissolution of metronidazole from sustained release floating tablets was studied with varied proportions of sodium bicarbonate (SB) and Pharmatose DCL 11. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. The variables studied include the matrices' release profile, hydration volume, and floating behavior. All Methocel matrices floated more than 8 h with SB proportions up to 24%, while Carbopol matrices floated more than 8 h with SB proportions only up to 12%. Matrices' hydration increased with time until reaching a peak and declining thereafter. Methocel matrices showed greater hydration volumes and greater drug dissolution compared to Carbopol matrices. After adding increasing quantities of Pharmatose to matrices containing 12% SB, hydration volume decreased while dissolution increased. These results were attributed to water-filled pores that formed following the Pharmatose dissolution and to reduced polymer proportions. Carbopol matrices showed greater susceptibility to the added Pharmatose, becoming more erodible and releasing higher quantities of metronidazole. The greater Carbopol susceptibility to added Pharmatose was attributed to its faster hydration. Methocel matrices hydrate rapidly only at the surface, delaying hydration and Pharmatose dissolution.

Effect of disintegrants with different hygroscopicity on dissolution of Norfloxacin/Pharmatose DCL 11 tablets.

This paper reports the effect of disintegrant hygroscopicity on dissolution of tablets obtained by compression at 85 MPa of mixtures of Norfloxacin and different proportions of a disintegrant (Starch 1500, PVP XL 10 or Croscarmellose sodium) and a diluent (Pharmatose DCL 11). Dissolution behavior was evaluated according to USP 23, apparatus 2 (paddle) at 50 rpm and using 750 ml acetate buffer solution of pH 4, at 37 degrees C, as medium. Norfloxacin added of increasing proportions, in a given range, of each disintegrant or the diluent increased the drug dissolved. Addition of increasing proportions of Pharmatose DCL 11 to Norfloxacin with 5% of the high hygroscopic Starch 1500 reduced the dissolution improvement effect of Pharmatose DCL 11. Addition of 5% Pharmatose DCL 11 to tablets of the middle hygroscopic Croscarmellose sodium and Norfloxacin slightly reduced the Croscarmellose sodium dissolution promoting effect, while addition of 15% Pharmatose DCL 11 to tablets of the low hygroscopic PVP XL 10 and Norfloxacin showed no inhibition but potentiated substantially the dissolution of Norfloxacin. These effects were attributed to competition for the available water in the tablet and to different water consume, for dissolution or hydration, by the diluent and the disintegrants.

High-performance liquid chromatography assay for indorenate in pharmaceutical powders.

A high-performance liquid chromatographic (HPLC) method for quantification of indorenate admixed of pharmaceutical excipients (Pharmatose DCL 21, Povidone USP and Helmcel 200) is described. Indorenate was extracted from the mixtures using a mobile phase composed of acetonitrile and a sodium acetate buffer solution 0.1 M (63:37) and separated from other dissolved components by ion supression-HPLC. The method was standardized using a C-18 column (250 mm x 4.8 mm, i.d., 5 microns). The photometric detector was fixed at 228 or 272 nm depending on the admixed excipients. Validation parameters included linearity, precision, accuracy, reproducibility, and specificity. The method was specific, selective, and capable to distinguish indorenate from their degradation products and the antihypertensive pelanserine.

Effect of carrier excipient and processing on stability of indorenate hydrochloride/excipient mixtures.

The purpose of this investigation was to determine the solid-state chemical stability of a model drug, indorenate hydrochloride, as a function of carrier excipient and mixing process. Physical mixtures and granules were prepared by tumble mixing and alcoholic granulation with and without binder. Stability of the mixtures was estimated using differential scanning calorimetry and isothermal degradation studies at 40, 50, and 60 degrees C. Average first-order degradation constants at 25 degrees C, extrapolated from isothermal studies, were much lower for indorenate hydrochloride after tumbling mixing with microcrystalline cellulose (3.45 x 10(-5) day-1) than those obtained after tumbling mixing with lactose (112.0 x 10(-5) day-1). Distribution of the drug on the excipient's surface, through granulation with and without Povidone, increased the average drug degradation rates in granules with microcrystalline cellulose (36.2 x 10(-5) day-1) as well as in granules with lactose (326 x 10(-5) day-1). Partially amorphous lactose (spray-dried lactose) showed higher average degradation rates (310.5 x 10(-5) day-1) than crystalline lactose (199.3 x 10(-5) day-1). It appears that the amorphous portion of the drug as well as that of reacting excipients play a major role in affecting the reaction rate. The calorimetric studies showed a strong solid-solid interaction between indorenate hydrochloride and lactose, suggesting chemical incompatibility. This strong solid-solid interaction was characterized by disappearance of typical transition peaks of lactose at temperatures above 200 degrees C and the development of new peaks at about 130-170 degrees C. No major changes in transition peaks were observed in mixtures of microcrystalline cellulose and indorenate hydrochloride, suggesting chemical compatibility. Calorimetric results allow the prediction of the chemical incompatibility between indorenate hydrochloride and lactose observed in isothermal degradation studies.