Razvoj i fizikokemijsko vrednovanje farmakosoma diklofenaka

Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80 %) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 1.1 %. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 µg mL1 as compared to 10.5 µg mL1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8 % while the free diclofenac acid showed a total of only 60.4 % drug release at the end of 10 h of the dissolution study.Farmakosomi su amfifilni lipidni vezikularni sustavi sa sposobnošću poboljšanja bioraspoloživosti lijekova slabo topljivih u vodi i organskim otapalima. U svrhu povećanja topljivosti diklofenaka (ljekovite tvari koja je slabo vodotopljiva, a uzrokuje i gastrointestinalnu toksičnost) pripravljeni su i evaluirani njegovi farmakosomi (fosfolipidni kompleksi). Diklofenak je kompleksiran s fosfatidilkolinom (80 %) u ekvimolarnom omjeru, u prisutnosti diklormetana, konvencionalnom metodom evaporacije. Tako pripravljenim farmakosomima ispitivana je topljivost, sadržaj ljekovite tvari, morfologija površine (pomoću pretražne elektronske mikroskopije), ponašanje pri prijelazu faza (pomoću diferencijalne pretražne kalorimetrije), kristaliničnost (rendgenskom analizom praha) i in vitro oslobađanje. Farmakosomi diklofenaka su nepravilnog oblika ili u obliku diska te imaju neravnu površinu u SEM-u. Sadržaj ljekovite tvari je 96,2 1,1 %. DSC termogrami i XRPD podaci potvrdili su nastajanje fosfolipidnog kompleksa. Topljivost u vodi dobivenih kompleksa bila je 22,1 µg mL1, a topljivost samog diklofenaka 10,5 µg mL1. Postignuto poboljšanje topljivosti može imati za posljedicu povećano oslobađanje i manju gastrointestinalnu toksičnost. Tijekom 10 h iz farmakosoma se oslobodilo 87,8 %, a iz slobodnog diklofenaka samo 60,4 % ljekovite tvari