The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 Ib. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (> or = 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.
The purpose of this study was to enhance the dissolution of mefenamic acid (MFA) through the formation of solid dispersion systems, and to compare the dissolution of the unformulated dispersions with those of formulated dispersions in tablets. Solid dispersions of MFA were prepared in polyethylene glycol 3350 (PEG) as a binary system, and PEG and Tween 20 (TW) as a ternary system by the melt method. The dispersions were characterized by dissolution, scanning electron microscopy, and powder x-ray diffraction studies. A decrease in MFA composition in the binary dispersion systems from 50 to 5% w/w resulted in a 50% increase in the dissolution rate during the period of study, and this was threefold higher than that of pure MFA. Incorporation of TW in the preparation of ternary dispersion systems resulted in a further increase in MFA dissolution. A sevenfold increase in MFA dissolution was observed when the ternary system composition was MFA/PEG/TW 4.7:93:2.3 (% w/w). Scanning electron microscopy and x-ray diffraction pictures showed an increase in size and decrease in crystallinity of the dispersions, respectively. Compression of the dispersions into tablets did not have any effect on the dissolution of the drug from the dispersions. Compression of pure MFA and Avicel PH 101, which was used as a diluent and disintegrant, resulted in a threefold increase in dissolution. However, the dissolution of the uncompressed mixture was identical to that of pure MFA. Thus, further processing of the solid dispersions into tablets did not decrease the rate of dissolution of the drug in the dispersions. This may be very important in the formulation of solid dispersions as tablets, which could lead to a reduction in the dose of practically water-insoluble drugs.
The purpose of this study was to use near-infrared spectroscopy (NIRS) as a nondestructive technique to (a) differentiate three Avicel products (microcrystalline cellulose [MCC] PH-101, PH-102, and PH-200) in powdered form and in compressed tablets with and without 0.5% w/w magnesium stearate as a lubricant; (b) determine the magnesium stearate concentrations in the tablets; and (c) measure hardness of tablets compressed at several compression forces. Diffuse reflectance NIR spectra from Avicel powders and tablets (compression forces ranging from 0.2 to 1.2 tons) were collected and distance scores calculated from the second-derivative spectra were used to distinguish the different Avicel products. A multiple linear regression model was generated to determine magnesium stearate concentrations (from 0.25 to 2% w/w), and partial least squares (PLS) models were generated to predict hardness of tablets. The NIRS technique could distinguish between the three different Avicel products, irrespective of lubricant concentration, in both the powdered form and in the compressed tablets because of the differences in the particle size of the Avicel products. The percent error for predicting the lubricant concentration of tablets ranged from 0.2 to 10% w/w. The maximum percent error of prediction of hardness of tablets compressed at the various compression forces was 8.8% for MCC PH-101, 5.3% for MCC PH-102, and 4.6% for MCC PH-200. The NIRS nondestructive technique can be used to predict the Avicel type in both powdered and tablet forms as well as to predict the lubricant concentration and hardness.
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