Da-Peng Wang

Formulation Development of Oral Controlled-Release Pellets of Diclofenac Sodium

AbstractIn this study, various formulations of controlled-release pellets of diclofenac sodium were prepared. Selected polymeric film coatings were applied to the drug-loaded nonpareils and their effects on the in vitro drug release from the multiple-unit dosage form were examined. It was found that a combination of ethylcellulose, myvacet 9–40, and talc produced a stable film coating and controlled drug release was achieved. Dissolution data demonstrated that this formulation produced predictable and reproducible drug data release characteristics.

Formulation Development of Allopurinol Suppositories and Injectables

Allopurinol was formulated into injectable and suppository dosage forms. The injectable formulation was prepared by dissolving allopurinol in a cosolvent system consisting of dimethyl sulfoxide (DMSO) and propylene glycol (v/v = 50/50). The stability of allopurinol in the cosolvent system was studied under accelerated storage conditions, and results indicate first-order degradation kinetics with an activation energy of 24.3 kcal/mol. The development of suppository dosage forms was performed by formulating allopurinol with polyethylene glycol (PEG) mixtures of different molecular weights. In vitro release profiles of suppositories formulated with different polyethylene bases were obtained in the pH 7.4 buffer solution using the USP 23 paddle method at 100 rpm. Results indicate that the release rate of the suppository formulations containing PEG 1500/PEG 4000 at the ratio (w/w) of 2.5/10 to 10/2.5 appeared to be similar. However, the addition of sodium lauryl sulfate in the suppository decreased the release rate of allopurinol significantly. A future study to establish in vitro/in vivo correlation (iv/ivc) is suggested.

High-Performance Liquid Chromatographic Determination of Ketoprofen in Pharmaceutical Dosage forms and Plasma

Abstract A high-performance liquid chromatographic (HPLC) method for determining ketoprofen in dosage forms and plasma is developed. The drug was chromatographed in a C18 column, using a mobile phase consisting of acetonitrile and 1 % acetic acid aqueous solution with ratio 40 : 60, and detected at 254 nm. The linear detector response to the concentration was confirmed. Recoveries from standard addition to tablets and nonaqueous solution were 100.43 and 100.15, for humans and for rabbit plasmas 82.4 and 82.7, respectively. The procedure showed excellent reproduction inside of two days. It is suggested that this HPLC method could be used for routine assay of ketoprofen in pharmaceutic dosage forms and plasma.

Percutaneous Transport of Diclofenac Sodium from Mixtures of Fatty Alcohol (or Fatty Acid) and Propylene Glycol Through the Rabbit Abdominal Skin

Diclofenac sodium is a nonsteroidal anti-inflammatory drug with analgesic, antipyretic, and anti-inflammatory activity. When used in a topical application, diclofenac can diffuse through the skin and into the subcutaneous tissue to effect the anti-inflammatory action. In this study, in vitro evaluations of the percutaneous transport of diclofenac sodium in various bases containing fatty alcohols/propylene glycol or fatty acid/propylene glycol mixtures through the abdominal skin of the rabbit were investigated. Results show that the transdermal flux of diclofenac sodium in the fatty alcohol/propylene glycol bases of the same ratio is affected by the chain length of the fatty alcohol, and its effect is in the order of C10 > C12 > C14 > C18. However, the transdermal flux of diclofenac sodium in the fatty acid/propylene glycol bases of the same ratio is also affected by the chain length of the fatty acid, but no absolute relationship was found. For the same chain length of fatty acid and fatty alcohol used in the formulation base that was otherwise the same, the transdermal flux of diclofenac sodium is higher in the formula containing fatty alcohol than that containing fatty acid.

Rapid fluorimetric assay for plasma nefopam using high-performance liquid chromatography

Abstract A simple and rapid liquid chxornatographic method for the determination of nefopam in plasma is presented. Plasma samples after de-protein management were directly analyzed by HPLC system with fluorimetric detector. The separation was achieved on a NOVA-PAK C18 column with a mixture of acetonitrile and 0.05M phosphate buffer at pH 3.0 using sodium propanesulfonate as the ion-pair agent. Low detection limit (0.5 ng) and linearity of calibration curve validate the suitability. Peak purity of nefopam in die chromatograms was checked by an additional photodiode-array detector (PAD). Recoveries of nefopam in plasma by de-protein and liquid-liquid extraction were 94.79 and 94.31%, respectively. In the in vivo iontophoresis study, remarkable differences of penetration effect were obtained . It is suggested that this HPLC method could be used for pharmacokinetic study of nefopam.

Development of Extended Release Dosage Forms Using Non-Uniform Drug Distribution Techniques

ABSTRACT Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37°C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

Formulation Optimization of Controlled-Release Pellets of Metoclopramide Hydrochloride Using Dissolution Fit Factor Approach

The purpose of this study was to optimize the formulation variables for the preparation of ethyl cellulose-coated nonpareils loaded with metoclopramide hydrochloride (MCL). The approach to evaluate the effectiveness of formulation parameters was monitored by release rate testing using dissolution fit factors as a tool. The content of ethyl cellulose used in the formulation was based on the drug-loaded weight. The interrelationship of each developed formulation and the reference formulation Gastro-Timelets® and their respective dissolution curves were evaluated using Moores equation: f2 = 50 × log {[1 + 1/n ∑nt = 1 Wt(Rt − Tt)2]−05 × 100}. The relationship between the ethyl cellulose content in the formulation and the dissolution fit factor f2 can be described as the following regression equation: Y = −0.054X2 + 3.347X − 1.915 (r2 = 0.99). The optimum ethyl cellulose content obtained from the equation was 30.8%. The type and content of plasticizer used in the formulation to achieve the greatest f2 were determined to be Myvacet 9–40 at the concentration of 25%. Results indicated that using the release rate testing approach with the dissolution fit factor as a tool could provide valuable information for formulation optimization.

Stability of 4-DMAP in solution.

A stability-indicating reversed-phase performance liquid chromatographic method was developed for the detection of 4-(N, N-dimethylamino)phenol (4-DMAP) and its degradation products under accelerated degradation conditions. The degradation kinetics of 4-DMAP in aqueous solution over a pH range of 1.12–6.05 and its stability in solutions based on propylene glycol or polyethylene glycol 400 were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pH rate profile shows that maximum stability of 4-DMAP was observed in the pH range 2.0 to 3.0. Acid/base catalysis of 4-DMAP was not affected by systems of various ionic strengths. Incorporation of nonaqueous propylene glycol or polyethylene glycol 400 in the pH 3.05 solution of 4-DMAP showed an increase in the stability at 55°C ± 0.5°C,

Stability of Cefazolin in Pluronic F-127 Gels

As a part of studies on the possible application of pluronic F-127 gels for drug delivery systems, an investigation was carried out to characterize cefazolin stability in aqueous pluronic F-127 gels. Pseudo-first-order rate constants for the cefazolin degradation were obtained from different concentrations of pluronic F-127 gels at temperatures of 35°, 45°, and 55°C. Rate measurements were also carried out in the gels composed of different pluronic F-127 concentrations (20%, 25%, and 30% w/v).

In Vitro Delivery of Fluocinolone Acetonide in FAPG Base

AbstractThe effects of oleic acid and lauric acid in a mixture of fatty alcohol and propylene glycol (FAPG base) on the percutaneous absorption of fluocinolone acetonide (FA) were investigated by using nude mouse skin and synthetic membrane in vitro. me mixture of 0.9% sodium chloride and methanol (91) was used as the receptor phase for the diffusion study. The concentration of FA in the receptor phase was determined by HPLC. fie optimal formulation of the FAPG base was obtained with the addition of 5% lauric acid