Abstract
Over the past few decades, the amorphous solid dispersions (ASDs) technique has emerged as a promising strategy to enhance the in vitro/in vivo characteristic of hydrophobic drugs. The low aqueous solubility and poor bioavailability of atorvastatin calcium (ATO), a lipid-lowering drug, present challenges for effective drug delivery. The objective of this work was to improve the aqueous solubility, in vitro dissolution, and oral absorption of ATO with amorphous solid dispersion technique prepared by spray-drying method. The optimized ternary formulation comprising of ATO; hydroxypropyl methylcellulose (HPMC), as a hydrophilic polymer; and sodium lauryl sulfate (SLS), as a surfactant, at a weight ratio of 1/1/0.1, showed significant improvement in aqueous solubility by ~18-fold compared to that of the free drug, and a cumulative release of 94.09% compared to a release of 59.32% of the free drug. Further, physicochemical studies via scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction revealed a change from the crystalline state of the free drug to its amorphous state in the ASD. Pharmacokinetic analysis in rats demonstrated 1.68- and 2.39-fold increments in AUC and Cmax, respectively, in the ASD over the free drug. Altogether, hydrophilic carrier-based ASDs prepared by the spray-drying technique represent a promising strategy to improve the biopharmaceutical performance of poorly soluble drugs.
Highlights
40% of new chemical entities identified in drug discovery programs have poor aqueous solubility [1,2]
Increase in surface area via particle size reduction, molecular dispersion of crystalline compounds into hydrophilic carriers resulting in improved wettability and enhanced porosity, and manipulation of the solid state of the drug substance, i.e., the transformation of a crystalline drug to its amorphous state, all of which result from use of Solid dispersion (SD) systems, leading to improved in vitro and in vivo drug characteristics [15]
Carrier selection plays a significant role in the performance of amorphous SDs, because the moleCcuarlariredrisspeleercstiioonnopf dlaryusgainstihgencifaircrainert mroulestiinnvtohlevepseirgfnoirfimcaanntcemoisfciabmiliotyrp, whoituhsstSrDonsg, bdercuagu–sceartrhieer minotelercaucltaiorndsis(pee.grs.,iohnyodfrodgrueng-binonthdeincga)rrfieorr mstuasbtiliintyvoalvgeaisnisgtnirfeiccarynsttmalliiszcaibtiiolinty,[3w6i,t3h7]s.troTnog ddreurigv–e ctahrerimeraixnitmeraalctaiodnvsan(eta.gg.e, hfyrodmrogaenn-AboSnDdisnygs)tefmor, stthaebicliatryriaegra’sinmstirseccibryilsittyallwiziatthiotnhe[3d6,r3u7g]. sThoodueldrivbee tihnevemstaigxiamteadl pardiovrantotafgoermfruolmatioann
Summary
40% of new chemical entities identified in drug discovery programs have poor aqueous solubility [1,2]. Increase in surface area via particle size reduction, molecular dispersion of crystalline compounds into hydrophilic carriers resulting in improved wettability and enhanced porosity, and manipulation of the solid state of the drug substance, i.e., the transformation of a crystalline drug to its amorphous state, all of which result from use of SD systems, leading to improved in vitro and in vivo drug characteristics [15]. Spray-drying is a commonly used solvent evaporation technique for the production of SDs and is extensively used in pharmaceutical industry. It mainly involves dissolving or suspending or drug and carrier(s), atomization of the solution/suspension, mixing and drying of liquid with a stream of heated air, and separation of the dried particles from the hot gas [16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
