Dozirani pripravci aceklofenaka za topičku primjenu: In vitro i in vivo karakterizacija

Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1 % m/m aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations.Aceklofenak je lijek nove generacije nesteroidnih protuupalnih lijekova sa izraženim protuupalnim i analgetskim djelovanjem. Dostupan je u obliku tableta od 100 mg. U ovom radu razvijeni su dozirani pripravci za topičku primjenu u svrhu smanjenja ili uklanjanja nuspojava povezanih s oralnom primjenom nesteroidnih protuupalnih lijekova. Ti pripravci mogu se upotrijebiti kao dodatak peroralnoj terapiji artritisa i srodnih bolesti. Opisana je priprava mazila, krema i gela s 1 % m/m aceklofenaka te njihova fizička svojstva, pH, mazivost, istiskivost, jednolikost sadržaja ljekovite tvari, difuzija i permeabilnost in vitro. Nakon analize rezultata za daljnja ispitivanja odabrani su gelovi pripravljeni na bazi Carbopola 940 (AF2, AF3) i makrogola (AF7). Ispitana je akutna iritacija kože, protuupalno i analgetsko djelovanje koristeći karagenom induciranu termičku hiperalgeziju i edem šape. Pripravak AF2 bio je značajno (p < 0,05) učinkovitiji u inhibiciji hiperalgezije s upalom nego pripravci AF3 i AF7. Stoga se AF2 može predložiti kao alternativa peroralnim pripravcima

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half–life of approximately 1 h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross–linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2 mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698 ± 2.34 to 769 ± 1.43 μm. The drug entrapment efficiency varied between 55.24 ± 4.61 to 82.29 ± 3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross–linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes

Synthesis and Antitubercular Activity of Some Novel Thiazolidinone Derivatives

Purpose: To synthesize and characterize novel thiazolidinone derivatives and screen them for antitubercular activity. Methods: A series of twelve novel thiazolidinones 4a-l have been synthesized by cyclocondensation of various Schiff bases of amino thiadiazole with thioglycollic acid. Various Schiff bases 3a-l were synthesized by condensation of 2-amino-5-aryl-5H-thiazolo[4,3-b]-l,3,4-thiadiazole with various aryl aldehydes. The synthesized compounds were characterized by FTIR, 1H-NMR, 13C-NMR and mass spectrometry. Docking studies were carried out for the synthesized compounds which were also evaluated for in vitro anti-tubercular activity at a concentration of 0.1-100.0 μg/mL by Microplate Blue Alamar Assay method. Pyrazinamide and streptomycin were used as standard antitubercular agents. Results: The synthesized compounds showed good docking score, compared to standard drugs. Two of the compounds (labelled 4f and 4i) showed higher antitubercular activity than the standards (pyrazinamide and streptomycin) while compounds four others compounds (labeled 4b, 4c, 4e, 4h, 4k and 4l) showed comparable activity to pyrazinamide but greater activity than streptomycin. Conclusion: We report the successful synthesis of novel thiazolidinones, as well as their spectral characterization, docking properties and in vitro antitubercular activities which, for some, are superior to currently used anti-tubercular agents