title: Formulation and in vitro/in vivo evaluation of terbutaline sulphate incorporated in PLGA (25/75) and L-PLA microspheres.
abstract: Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (L-PLA) were chosen as matrix materials. A solvent evaporation method was used for preparation of microspheres. Surface morphology, particle size distribution and encapsulation efficiency were investigated. In vitro release studies were performed in pH 7.4 phosphate buffer. In vitro distribution of microspheres were studied in the Swiss albino male mice. All microspheres were spherical in shape and had a porous surface with mean diameters of 9-21 microm. The encapsulation efficiency was influenced by the polymer type, but not the molecular weight. About 90% of the initial amount was trapped in PLGA microspheres, and the remainder was on the surface. In the case of L-PLA, 50% of the total drug was associated with the surface of microspheres. The In vitro release pattern was biphasic characterized by an initial burst phase followed by a slower phase. The L-PLA microspheres released approximately 92% of the initial payload in 72 h. On the other hand, TBS release was increased with an increase in the molecular weight of PLGA. Biodistribution of L-PLA microspheres was characterized by an initially high uptake (35%) by the lungs. All these results suggest that L-PLA and PLGA microspheres have the potential to be used for passive lung targeting.
authors.affiliation: Faculty of Pharmacy, Hacettepe University, 06100-Ankara, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Selek
authors.forename: S
authors.initials: S
authors.lastname: Sahin
authors.forename: M T
authors.initials: MT
authors.lastname: Ercan
authors.forename: M
authors.initials: M
authors.lastname: Sargon
authors.forename: A A
authors.initials: AA
authors.lastname: Hincal
authors.forename: H S
authors.initials: HS
authors.lastname: Kas
mesh_terms: D001673:Biodegradation, Environmental; D001704:Biopolymers; D001993:Bronchodilator Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002850:Chromatography, Gel / Q000379:methods; D019344:Lactic Acid; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012995:Solubility; D013726:Terbutaline / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D001704:Biopolymers; D001993:Bronchodilator Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013726:Terbutaline