Levent Kirilmaz

Extended release lipophilic indomethacin microspheres: formulation factors and mathematical equations fitted drug release rates

Extended release liphophilic microspheres of indomethacin were prepared using cetostearyl alcohol (CsA), stearyl alcohol (SA) and cetyl alcohol (CA) in the various drug-lipid ratios. The release of indometacin was studied on the basis of USP criteria and the effects of drug-lipid ratio, the size of microspheres and carboxymethylcellulose sodium (CMC-Na) added as a hydrophilic polymer on the drug release were investigated. In vitro dissolution studies were performed using USP XXIII apparatus I at pH 6.2. Release profiles were evaluated according to first order, Higuchi square root of time and Hixson-Crowell cube root models. The best fit was found with the square root of time model (r2=0.991) for the microspheres (125-250 microm) prepared in 1:4:1 drug-lipid-copolymer ratio using stearyl alcohol. With a further regression analysis, an excellent equation (Release%=-10.721+42.549*square root of (t)-4.027*t) was developed for empirical drug estimation (r2=0.998).

Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration

Objective: To evaluate the effects of adjunctive meloxicam administration on clinical periodontal measurements and gingival crevicular fluid (GCF) prostaglandin E2 (PGE2) and interleukin-1-beta (IL-1β) levels in chronic periodontitis. Methods: Forty chronic periodontitis patients were randomized to receive either meloxicam 7.5 mg or placebo tablets for 10 days with scaling and root planing (SRP). GCF levels of PGE2 and IL-1β at baseline, day 10 of drug intake and 4 weeks after SRP were determined by enzyme-linked immunosorbent assay. Demographic, clinical periodontal data were analyzed using a repeated measures ANOVA and Bonferroni analysis. GCF PGE2 and IL-1β levels were compared between different evaluation times using the Friedman test. The Mann–Whitney test was used to compare biochemical data between the study groups. Pearson correlation analysis was used to relate clinical and biochemical data. Results: Study groups showed significant reductions in all clinical periodontal measurements and GCF volume (p < 0.05). In both groups, IL-1β was reduced significantly on day 10 and at week 4 compared with baseline (p < 0.01) without significant changes in PGE2 levels (p > 0.05). No significant differences were found between study groups in GCF IL-1β or PGE2 levels (p > 0.05). Conclusion: Adjunctive meloxicam does not seem to provide additional improvement in clinical parameters or GCF PGE2 and IL-1β levels. Larger-scale studies may better clarify potential usage of anti-inflammatory agents in periodontal therapy.

Evaluation of in vitro release and skin irritation of benzoyl peroxide-containing products

Abstract Benzoyl peroxide (BPO) has been known as a highly effective topical agent in acne vulgaris therapy for a long time. It induces an irritant dermatitis with erythema and scaling. Therefore, the aim of this study was to formulate BPO containing w/o/w multiple emulsion and gel formulations with and without chitosan microparticles to decrease skin irritation and to compare the release profiles through cellulose acetate, cellophane membranes and excised rat skin. A commercial preparation was also used and the similarities between commercial and experimental formulations were assessed by difference factor (f). The release results indicated that gel base exhibited a higher drug release than the other experimental formulations (p

Sustained-release dosage form of oxolamine citrate: preparation and release kinetics

One of the principal uses of microencapsulation for pharmaceuticals has been the preparation of sustained-release dosage forms which have been usually presented in the form of a suspension or gel. However, a non-disintegrating tablet would be a better formulation to obtain sustained-release effect. Microencapsulation has been employed to provide protection of the core material against atmospheric effects, to cover the unpleasant taste and to enhance the stability. A number of drugs have also been encapsulated to reduce gastric and other GI tract irritations, to alter release properties and to change availability. Oxolamine citrate is one of the synthetic derivatives of 3,5-disubstituted 1,2,4-oxodiazole, used particularly for its antitussive activity. The usual dose of the drug is 200 mg given four times a day. Its use was limited by side-effects of nausea and vomiting. In order to prevent the disadvantages caused by taking the drug four times daily, and to reduce the side-effects, a sustained-release dosage form of oxolamine citrate was prepared by the microencapsulation technique and microcapsules thus formed were pressed into tablets. Dissolution tests were done with microcapsules and tablets formed by microcapsules by using the USPXXI paddle method and dissolution kinetics were studied and evaluated.

A Novel Pilocarpine Microemulsion as an Ocular Delivery System: In Vitro and In Vivo Studies

Despite several disadvantages like a rapid wash out and dilution of the formulation leading to a low bioavailability, eye drops are the most commonly used dosage form for the ocular route. Due to their properties and numerous benefits, microemulsions are promising systems for topical drug delivery. The purpose of this work is to develop a suitable ocular microemulsion formulation with adequate physicochemical stability for enhancing the bioavailability of pilocarpine. Physicochemical characteristics of the microemulsion including the drug content, refractive index, conductivity, viscosity, intraocular pressure (IOP) and ocular tolerance were investigated. The ocular irritation test and the IOP lowering activity of the microemulsion were studied in New Zealand white rabbits. The developed formulation showed good physicochemical properties and a beneficial stability for six months. After microemulsion instillation into the rabbit eyes, the intraocular pressure was reduced significantly. The ocular irritation test used suggested that microemulsion formulation did not cause any significant allergies to the eye.

Novel application of Eudragit RL and cholesteryl oleyl carbonate to thermo-sensitive drug delivery system

The Eudragit RL 100 and propylene glycol (PG) membranes with and without cholesteryl oleyl carbonate (COC) were prepared by the solvent casting method to pioneer a novel application of a thermo-sensitive drug delivery system. After that, the properties of these membranes were investigated by thermal, scanning, and porosity studies. Drug permeation studies through all membranes were carried out using salbuthamol sulphate (SBS) at constant temperatures (25°C and 37°C), respectively. The permeability of SBS through the membranes with COC has been shown to be a discontinuous function of temperature, that is, their permeability increased steeply above the phase transition temperature (37°C) of the COC. The thermo-sensitive permeation mechanism for the membranes might be based on the structure change of the membranes caused by the phase transition, so that the membranes could absorb more water. Considering the high biological safety of Eudragit RL 100 and PG membranes with and without COC might be used to develop a novel thermo-sensitive drug delivery system.

Novel microparticle drug delivery systems based on chitosan and Eudragit®RSPM to enhance diltiazem hydrochloride release property

The aim of this study was to enhance the release properties of diltiazem hydrochloride (diltiazem HCl) by using microparticle system. For this reason, microparticle drug delivery systems based on chitosan and Eudragit®RSPM were developed. The microparticles were prepared by using double-emulsion solvent extraction method and the mean sizes of microparticles were less than 120 µm. The in vitro drug release from microparticles was studied in simulated gastric (pH 1.2) and intestinal media (pH 7.4) than the results were evaluated by kinetically. In vitro diltiazem HCl release from microparticles showed good zero order kinetic. For the microparticles with chitosan, the release of diltiazem HCl at pH 1.2 could be effectively sustained, while the release of diltiazem HCl increased at pH 7.4 when compared to Eudragit®RSPM microparticles. The highest release percent obtained was 1:1 ratio of drug: polymer at pH 1.2 and 7.4. All results clearly suggest that the release properties of diltiazem HCl were improved by using microparticle systems especially which contain chitosan.

Relationships Between Serum Triglyceride Concentration and Abdominal Fat Weight of Broilers

Abstract Settar, P., Akbas, Y., Kirilmaz, L. and Yalcin, S. 1998. Relationships between serum triglyceride concentration and abdominal fat weight in broilers. J. Appl. Anim. Res., 14: 29–32. To investigate the relationship between abdominal fat weight and serum triglyceride concentration, pedigreed chicks of 10 sire families were used. Blood samples were collected at 56 d and birds were slaughtered. Serum triglyceride concentration was similar in males (47.6±3.2) and females (53.4±3.5). A significant phenotypic correlation between relative abdominal fat weight and serum triglyceride levels was observed.