Ahmad Bani-Jaber

Sustained Release Characteristics of Tablets Prepared with Mixed Matrix of Sodium Carrageenan and Chitosan: Effect of Polymer Weight Ratio, Dissolution Medium, and Drug Type

The interpolymeric complexation of carrageenan and chitosan was investigated for its effect on drug release from polymeric matrices in comparison to single polymers. For this purpose, matrices with carrageenan: chitosan (CG:CS) ratios of 100%, 75%, 50%, 25%, and 0% were prepared at 1:1 drug to polymer ratio. The effect of dissolution medium and drug type on drug release from the formulations was addressed. Two model drugs were utilized: diltiazem HCl (DZ) as a salt of a basic drug and diclofenac Na (DS) as a salt of an acidic drug. Three dissolution media were used: water, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). Some combinations of the two polymers showed remarkable sustained release effect on DZ in comparison to the single polymers in water and SGF. However, no apparent effect for the combination on DZ release was shown in SIF. The medium effect was explained by the necessity of chitosan ionization, which could be attained by the acidic SGF or microacidic environment created by the used acidic salt of DZ in water, but not in SIF. An interaction between the medium type and CG:CS ratio was also found. With DS, the polymer combinations had similar dissolution profiles to those of the single polymers in water and SIF, which was explained by the lack of chitosan ionization by the medium or the drug basic salt. The dissolution profiles could not be obtained in SGF, which was attributed to the conversion of DS into diclofenac free acid. The importance of chitosan ionization for its interaction with CG to have an effect on the release of DS was demonstrated by performing dissolution of SGF presoaked tablets of DS in SIF, which showed an effect of combining the two polymers on sustaining the drug release.

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug–protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

Diclofenac-bismuth complex: Synthesis, physicochemical, and biological evaluation

Diclofenac-bismuth complexation was attempted by mixing diclofenac sodium (Na) and bismuth-subcitrate aqueous solutions at diclofenac:bismuth molar ratio of 3:1. A solid precipitate was obtained and isolated. The precipitate was characterized for stoichiometric ratio of diclofenac-bismuth complexation using capillary electrophoresis, which showed 1:1 complexation. In addition, nuclear magnetic resonance and Fourier transform infrared analysis were performed for the isolated solid complex and indicated that bismuth was in coordinate bond formation with the carboxylate group of diclofenac. In comparison with diclofenac Na powder, the complex was evaluated as an aqueous suspension for in vitro drug dissolution. The complex exhibited a faster dissolution rate than and similar dissolution extent as diclofenac Na. In comparison with an aqueous solution of diclofenac Na and an aqueous suspension of physical mixture of diclofenac acid (suspended) and bismuth-subcitrate (dissolved), the aqueous complex suspension was evaluated for ulcerogenic effect in rats upon oral administration. The complex led to more gastric ulceration than diclofenac Na, which was not in accordance with the antiulcer properties of bismuth. This antiulcer effect was shown as the physical mixture administration was accompanied with lower gastric ulceration than diclofenac Na administration. These gastric ulceration results were explained in terms of the difference in particle size between solid diclofenac acid formed as a result of the complex breakdown in an acidic medium (0.1 M HCl to simulate the gastric fluid) and that formed as a result of diclofenac Na neutralization. Diclofenac acid particles formed from the complex breakdown were of average size, three times smaller of those formed as a result of diclofenac Na protonation. This difference in particle size was correlated with the higher gastric ulceration associated with the complex than with diclofenac Na in terms of higher coverage of the gastric mucosa with diclofenac, and consequently, higher local ulceration.

A newly developed lubricant, chitosan laurate, in the manufacture of acetaminophen tablets.

To study the usefulness of chitosan laurate (CS-LA), a newly developed chitosan salt, as a lubricant, lubrication properties such as the pressure transmission ratio and ejection force were determined at different concentrations of CS-LA in tableting. In addition, tablet properties such as the tensile strength, disintegration time, and dissolution behavior, were also determined. When CS-LA was mixed at concentrations of 0.1%-3.0%, the pressure transmission ratio was increased in a concentration-dependent manner, and the value at a CS-LA concentration of 3% was equal to that of magnesium stearate (Mg-St), a widely used lubricant. Additionally, a reduction in the ejection force was observed at a concentration from 1%, proving that CS-LA has good lubrication performance. A prolonged disintegration time and decreased tensile strength, which are known disadvantages of Mg-St, were not observed with CS-LA. Furthermore, with CS-LA, retardation of dissolution of the drug from the tablets was not observed. Conjugation of CS with LA was found to be quite important for both lubricant and tablet properties. In conclusion, CS-LA should be useful as an alternative lubricant to Mg-St.

The Synthesis and Characterization of Fatty Acid Salts of Chitosan as Novel Matrices for Prolonged Intragastric Drug Delivery

The aim of this study was to prepare fatty acid salts of chitosan (CS) and to evaluate the salts as matrices for sustained drug release and prolonged gastric retention. CS-laurate and CS-palmitate were formed by mixing saturated CS solution and aqueous solutions of sodium laurate and sodium palmitate, respectively, and collected by centrifugation. They were characterized using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Different matrices as effervescent tablets were prepared using each of these CS-salts, CS and the corresponding physical mixtures of CS and the fatty acids. Sodium bicarbonate as an effervescent agent and ranitidine HCl as a model drug were incorporated into these matrices. In vitro buoyancy and drug dissolution were studied for the matrices in 0.1 M HCl. Tablets with fatty acid salts of CS showed both rapid and prolonged buoyancy (> 8 h). Comparatively, CS tablets exhibited a short floatation period (< 2 h) and tablets were completely disintegrated within 1 h of soaking. In addition, slow and prolonged drug release was achieved from tablets of fatty acid salts of CS with average drug release of 80.1 and 71.8% for CS-laurate and CS-palmitate, respectively. Rapid drug release (> 80% at 1 h) was exhibited by tablets with CS or the physical mixtures.

Preparation and Evaluation of Newly Developed Chitosan Salt Coating Dispersions for Colon Delivery without Requiring Overcoating.

Although chitosan (CS) has been recognized as a good material for colon-specific drug delivery systems, an overcoating with an enteric coating polymer on the surface of CS is absolutely necessary because CS is soluble in acidic conditions before reaching the colon. In the present study, to improve its stability in the presence of acid, a newly developed CS-laurate (CS-LA) material was evaluated as a coating dispersion for the development of colon-specific drug delivery systems. Two types of CS with different molecular weights, CS250 and CS600, were used to prepare CS-LA films by the casting method. The CS250-LA films had smooth surfaces, whereas the surfaces of the CS600-LA films were rough, indicating that the CS250-LA dispersion could form a denser film than CS600-LA. Both of these CS-LA films maintained a constant shape over 22 h in a pH 1.2 HCl/NaCl buffer, where the corresponding CS films rapidly disintegrated. In addition, the CS250-LA film showed specific colon degradability in a pH 6.0 phosphate buffered solution containing 1.0% (w/v) β-glucosidase. As a result of tensile strength and elongation at the break, both CS-LA films were found to have flexible film properties. Finally, the release of acetaminophen from disks coated with CS250-LA dispersions was significantly suppressed in fluids at pH 1.2 and 6.8, whereas disks coated with CS solution rapidly released the drug in pH 1.2 fluids. Taken together, this study shows that LA modification could be a useful approach in preparing CS films with acid stability and colonic degradability properties without requiring overcoating.