Formulation and development of extended-release micro particulate drug delivery system of solubilized rifaximin.

Rifaximin (RFX), a semi-synthetic antibiotic belonging to BCS class IV category, has been used in the treatment of traveler's diarrhea. An attempt has been made to improve aqueous solubility of RFX in the presence of ß-cyclodextrin (ß-CD) and hydroxy propyl ß-cyclodextrin (HP-ß-CD) and control its release in the gut by enteric coating. The stoichiometric proportion of RFX and complexing agent's ß-CD and HP-ß-CD were determined by phase solubility studies. RFX-ß-CD and RFX-HP-ß-CD were prepared in 1:2 ratio by solvent evaporation technique using rota-evaporator with yield of 78% and 84% respectively followed by their evaluation using different techniques such as saturation solubility, Fourier transform infrared, differential scanning calorimeter, powder X-ray diffractometer, in vitro antimicrobial activity. The saturation solubility of RFX had improved from 0.0736 mg/ml to 0.2354 mg/ml and 0.5681 mg/ml in presence of ß-CD and HP-ß-CD respectively resulting in an increased zone of inhibition in the later complex during antimicrobial studies. The RFX-HP-ß-CD complex particles were coated with eudragit L 100 (EL 100) by spray drying technique. The 3(2) factorial design was applied to formulate the micro particles. All formulations exhibited pH dependant drug release. The % EE was 69% and the release of RFX was retarded by enteric coating in the optimized batch FB2. Therefore, it can be concluded that solubility of some BCS class IV drugs can be improved by ß-CD complexation and release of such inclusion complexes can be retarded to increase the residence time of RFX in the gastrointestinal tract.

Reduced ulcerogenic potential and antiarthritic effect of chitosan-naproxen sodium complexes.

The purpose of this research was to address the utility of naproxen sodium-chitosan spray-dried complexes for antiulcer and antiarthritic activities. The cold stress technique was used to examine the ulcerogenic potential of naproxen sodium (NPX) and spray-dried formulations in the different doses. The ulcerations reduced with the dose of spray-dried complexes of naproxen sodium and chitosan. The conspicuous hemorrhagic lesions were visible in the morphological features of the animal treated with naproxen 50 mg/kg (p.o.). Thus, the results suggest that the spray-dried naproxen sodium-chitosan complex (NPXF) was not corrosive to the gastric mucosa at high doses of 50, 100, and 200 mg/kg (p.o.) under stressful conditions. It is evident from the present investigation that NPXF does not possess any ulcerogenic potential in comparison to naproxen which, under stressful conditions, led to the hypersecretion of HCl, culminating to petichial hemorrhages in the gastric mucosa of the animals. The biphasic pattern was observed in the various arthritic parameters. The rise in paw volume, joint diameter, WBC count, arthritis score, and fall in body weight was significantly ameliorated in the animals treated with NPXF (5, 10, and 20 mg/kg, p.o). At the end of the study, slight erythema was visible in the naproxen-treated animals. However, no erythema, redness, or ulcers were visible in the animals treated with NPXF. Thus, the direct compression properties and reduced ulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability toward the drug, make naproxen sodium-chitosan spray-dried complexes particularly suitable for developing a reduced-dose, fast-release, solid oral dosage form of naproxen.

Effect of oppositely charged polymer and dissolution media on rheology of spray-dried ionic complexes.

The purpose of this research was to address the utility of rheological study in understanding the influence of oppositely charged polymers on release of naproxen sodium encapsulated in chitosan particles. The interaction between oppositely charged kappa-carrageenan (kappa-Ca) and chitosan leads to relatively higher gel strength, which is proportional to the ability to retard the drug release at acidic pH. The oscillatory tests within the linear viscoelastic range where the stress is proportional to the applied strain were performed on the hydrated sample matrices containing chitosan-naproxen sodium spray-dried complexes and k-Ca or hydroxypropyl methylcellulose (HPMC) in various ratios. It was observed that the effect of pH change on the dynamic moduli in spray-dried complexes containing kappa-Ca was much stronger than that with HPMC reflecting presence of strong ionic interaction between kappa-Ca and chitosan. The combination of oppositely charged polymers in different ratios proved to be useful in modulating the rheological properties of the hydrated formulations and their release-retarding properties. Dynamic moduli can be used to measure gel strength and are significant for the interpretation of oral sustained release spray-dried complexes.

Effect of drying methods on swelling, erosion and drug release from chitosan-naproxen sodium complexes.

The purpose of this research was to explore theapplication of ionic interactions between naproxen sodium (NS) and chitosan (CH) in complexes (NSC) prepared by tray drying (TD) and spray drying (SD) methods. Drug-polymer ratio (1:1) in the NSC was optimized on the basis of dialysis studies. The particulate systems of NSC were prepared by tray drying (TD) and spray drying (SD) methods. Release retarding polymers were added to the NSC and to the physical mixtures containing NS-CH and their effects on water uptake, matrix erosion and drug release at different pH were compared. Spray dried complexes (SDC) were spherical, free flowing, light and fine amorphous particles in contrast to the crystalline, hard, tenacious, irregularly shaped, denser tray dried complexes (TDC) with poor flowability. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) patterns confirm the conversion of crystalline to high energy amorphous phase suitable for ionic interactions in NSC. Presence of release retarding polymers, kappa carrageenan and hydroxypropylmethylcellulose (HPMC) in the NSC compacts retarded the drug release and improved the matrix integrity. Carrageenan matrices exhibited more retardation than HPMC tablets. FTIR patterns, erosion, swelling and drug release from matrices support ionic interactions between NS and CH in NSC. The reasons for retarded drug release from the chitosan matrices at acidic pH include poor solubility of drug at acidic pH, formation of a rate limiting polymer gel barrier along the periphery of matrices and the ionic interactions between oppositely charged moieties.

Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices.

The reasons for retarded release of naproxen sodium from the chitosan matrices at different pH include poor aqueous solubility of drug, the formation of a rate-limiting polymer gel barrier along the periphery of matrices, the interaction of naproxen sodium with protonated amino groups of chitosan, and the interaction of ionized amino groups of chitosan with ionized sulfate groups of kappa-carrageenan.