Karrar Ahmad Khan

Relationship between swelling, erosion and drug release in hydrophillic natural gum mini-matrix formulations

The swelling, erosion and solvent front penetration properties of mini-matrices containing xanthan (X), locust bean (LB) and karaya (K) gums were examined, analysed and related to the overall in vitro release kinetics of diclofenac sodium, used as a model drug. Mini-matrices were produced with drug:gum ratios of 1:1 as well as formulations of drug and X in combinations of 2:1, 2:3 and 1:2. The rank order of decreasing swelling index (SI) in both axial and radial dimensions was X?K?LB and each gum showed almost Fickian swelling behaviour. The solvent front penetration rates were consistent with the rates of swelling. However, the order of decreasing drug release and erosion rates was LB>X>K and all formulations demonstrated anomalous (non-Fickian) drug release kinetics. Therefore Fickian drug diffusion and polymer erosion were both occurring simultaneously. The dominant mechanism depended on the nature and content of the gum, as well as the stage in the dissolution time period. There was a loss of matrix integrity in formulations containing a high drug:gum ratio.

Development and evaluation of a multiple-unit oral sustained release dosage form for S(+)-ibuprofen: preparation and release kinetics

Mini-matrix tablets containing S(+)-ibuprofen have been prepared by the wet granulation method. The hydrophilic matrix was formed with either xanthan gum, karaya gum or hydroxymethylcellulose (HPMC) together with a choice of additives from lactose, Encompress(R), Avicel(R) PH101, talc and Lubritab(R). Multiple unit dosage forms (MUDFs) were subsequently obtained by encapsulating the mini-matrix tablets into hard gelatin capsules. Preparation, in vitro release profiles and release kinetics are presented.

Release characteristics of diclofenac sodium from encapsulated natural gum mini-matrix formulations

In attempts to design an oral sustained release multiple-unit dosage form for diclofenac sodium (D), we evaluated the use of four natural hydrophilic gums as mini-matrix formulations enclosed in a hard gelatin capsule. Carrageenan (C), locust bean (LB), karaya (K) and xanthan gums (X) were used to produce mini-matrices (3, 4.5 and 5.5 mm in diameter) containing a gum and D, and also with other release-regulating excipients in different proportions, namely lactose (L), Encompress® (E), cellulose acetate phthalate (CAP) and Veegum F® (V). The release profiles from several encapsulated mini-matrices in buffered dissolution medium (pH 7.0) showed that sustained release of D up to 77% of drug content was achieved from mini-matrices containing LB, X and K, while C did not produce sufficient sustained release. The calculated release exponents (n values) indicated that release behaviour was anomalous (non-Fickian). Polymer swelling and relaxation were both involved in the release process. For X, the drug release rate declined linearly with progressive increase in gum content but without changing the release behaviour. Maximum release from individual mini-matrices was > 90% and approaching zero-order release kinetics (n → 1). This was due to the larger surface area to volume ratio which provided an optimum balance between the diffusion and dissolution mechanisms. Solubility differences between the excipients did not affect the release rate, but increasing proportions of each excipient produced a faster release rate with the release mechanism changing from anomalous to Case II and then to Super Case II transport. The amount of gum present appeared to play the dominant role in determining the drug release rate.

A Simple and Rapid Method for the Quantification of Eudragit RS100 and RL100 Poly(methacrylates) in Sustained-Release Dosage Forms

A colorimetric ion-pair complexation method has been developed which provides a simple and rapid way of quantifying Eudragit RS100 and RL100 in pharmaceutical dosage forms. The quaternary ammonium groupings in these polymers appear to form an ion-pair complex with the dye tropaeolin OOO. When extracted into an organic phase, the optical density at 484 nm is linearly related to polymer concentration. Control of pH is important, and it should be maintained within the range 4.5 to 9.0. A wide range of pharmaceutical excipients commonly used in tablet, pellet, and film-coating formulations did not interfere with formation of the complex, but certain drugs were found to significantly enhance or decrease the assay response. Good reproducibility, precision, and accuracy were demonstrated when the method was applied to a film-coated pellet formulation containing an interfering drug (promethazine hydrochloride). However, removal of interfering substances must be optimized. The method was sufficiently sensitive for the determination of polymer on a single dose unit of encapsulated beads.