title: A novel injectable in situ forming poly-DL-lactide and DL-lactide/glycolide implant containing lipospheres for controlled drug delivery.
abstract: One of the greatest challenges in in situ forming implant (ISFI) systems by polymer precipitation is the large burst release during the first 1-24 hours after implant injection. The aim of this study was to decrease the burst-release effect of a water-soluble model drug, donepezil HCl, with a molecular weight of 415.96 Da, from in situ forming implants using a novel in situ implant containing lipospheres (ISILs). In situ implant suspensions were prepared by dispersing cetyl alcohol and glyceryl stearate lipospheres in a solution of poly-DL-lactide (PDL) or DL-lactide/glycolide copolymer (PDLG). Also, in situ implant solutions were prepared using different concentrations of PDL or PDLG solutions in N-methyl-2-pyrrolidone (NMP). Triacetin and Pluronic L121 were used to modify the release pattern of donepezil from the in situ implant solutions. In vitro release, rheological measurement, and injectability measurement were used to evaluate the prepared in situ implant formulae. It was found that ISIL decreased the burst effect as well as the rate and extent of drug release, compared to lipospheres, PDL, and PDLG in situ implant. The amount of drug released in the first day was 37.75, 34.99, 48.57, 76.3, and 84.82% for ISIL in 20% PDL (IL-1), ISIL in 20% PDLG (IL-2), lipospheres (L), 20% PDL ISFI (I5), and 20% PDLG ISFI (I8), respectively. The prepared systems showed Newtonian flow behavior. ISIL (IL-1 and IL-2) had a flow rate of 1.94 and 1.40 mL/min, respectively. This study shows the potential of using in situ implants containing lipospheres in controlling the burst effect of ISFI.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Soad A
authors.initials: SA
authors.lastname: Yehia
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Elshafeey
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Elsayed
mesh_terms: D000077265:Donepezil; D016503:Drug Delivery Systems; D007189:Indans / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D010880:Piperidines / Q000008:administration & dosage*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D007189:Indans; D008081:Liposomes; D010880:Piperidines; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D000077265:Donepezil