Naslov
Novel cyclodextrin-based chronopharmaceutical for zaleplon delivery

Autori
Jablan, Jasna ; Kujundžić, Nikola ; Jug, Mario

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstract / Bucar, Franz ; Schmid, Martin - Graz, 2014

Skup
23rd Scientific Congress of the Austrian Pharmaceutical Society

Mjesto i datum
Graz, Austrija, 23.04.2014. - 25.04.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
zaleplon; eudragit; pH responsive microspheres; cyclodextrin

Sažetak
The aim of this work was to develop pH-responsive microspheres of zaleplon (ZAL) with delayed drug release in the ileum, as a novel chronopharmaceutical drug delivery system, suitable for treatment of a specific type of insomnia characterised by premature awaking and inability to fall asleep again. ZAL is rapidly cleared from the body (t1/2=1h), therefore it would be suitable for development of such formulation [2]. Eudragit® L100 (EL100), a 1:1 methacrylatic acid/methylmethacrylate copolymer, with pH dependent solubility (pH>6) was used as the base of this formulation. Microparticles were prepared by spray-drying of ZAL/EL100 dispersion from ethanolic medium (MS1) or from 0.96% aqueous NH4HCO3 solution (MS2), transforming EL100 into soluble, thermolabile ammonium salt. In second case, after spray-drying procedure, EL100 was regenerated by thermal treatment at 85° for 3.5h, eliminating completely soluble ammonium salt from the microparticles, as confirmed by FTIR analysis. All microparticles prepared contained 10 mg dose of ZAL. Preparation method from ethanolic medium (MS1) resulted in higher preparation yield compared to other procedure used (75.14% vs. 56.55% ; p<0.05), while in both cases similar encapsulation efficiency of 95.5-99.6% and mean particle diameter of 1.62-1.76 μm were achieved. However, MS1 were characterised by significant drug leaking in the simulated gastric medium (81.7±2.2% of encapsulated drug dose in 2h at pH 1.2), while MS2 formulation released about 24.7±0.5% of ZAL under the same conditions (p<0.01). DSC and XRPD analysis showed that these results could be attributed to a thermally induced amorphization of ZAL into EL100 matrix, which was significantly pronounced when spray-drying feed was prepared in ethanolic medium. Therefore MS2 formulation was further optimised through addition of glyceryl monostearate (GMS), which sufficiently reduced unwanted drug release in simulated gastric medium to only 1.1±0.3% of encapsulated drug dose, but in the same time, reduced significantly the drug release rate in simulated intestinal medim (pH 6.8) to only 19.1 μg/min. To overcome this obstacle, randomly methylated β-cyclodextrin (RAMEB) was added to the feed solution in quantities which would result in complexation of 25, 50 and 100% of the drug dose. The presence of RAMEB did not change significantly the yield, encapsulation efficiency or mean spherical diameter of microspheres prepared, but influenced significantly, in dose dependent manner, on the in vitro release properties of ZAL from prepared microspheres. The optimal MS formulation contained 50% of the drug dose in form of inclusion complex with RAMEB, resulting in an acceptable drug release level in the simulated gastric medium (pH 1.2) of about 10% of the ZAL doze after 2h and a zero-order release (r2>0.98, k=155.0 μg/min) in simulated intestinal medium (pH 6.8).

Izvorni jezik
Engleski

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