ELSEVIER International Journal of Pharmaceutics 142 (1996) 135-142 Research papers Preparation and evaluation of insulin-loaded poly(DL-lactide) microspheres using an experimental design Isabel Soriano, Carmen Evora, Matias Llabr6s* Departamento de Ingenieria Quimica y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad de la Laguna, 38200 La Laguna, Tenerife, Spain Received 4 April 1996; accepted 29 May 1996 Abstract Twenty formulations of bovine insulin in poly(DL-lactide) (DL-PLA) microspheres were elaborated to study the influence of polymer molecular weight, insulin content and polyvinylalcohol (PVA) concentration on microsphere characteristics and in vitro release profile. Ten of them released nearly all the incorporated insulin in 24 h. Of the rest, four were porous, presenting a burst effect over 40% and releasing 70% in 48 h. The other six formulations were non-porous; four released the insulin in 1 week and the other two only released 28% in 15 days. None of these 10 formulations were able to release the total amount of incorporated insulin, probably due to the adsorption of insulin by the polymer. From the results obtained with the experimental design, one more lot was prepared and tested in vitro and in vivo. The in vitro release profile was much slower than the in vivo one; 16% and 28°/,, were released in vitro on the first day and in the following 10 days, respectively, while the corresponding figures for in vivo release were 60% and 90%. Ke),words: Insulin; Poly(DL-lactide); Microspheres; Prolonged release; In vitro in vivo comparison 1. Introduction Most peptides and proteins are not well ab- sorbed by the oral route since they lose potency in * Corresponding author. the digestive tract and they must be administered parenterally. The treatments for which these ther- apeutic agents are prescribed require stable levels over prolonged periods, which has led to the development of sustained release systems. In recent years, interest has focused on the use of microspheres prepared from polyesters such as poly(DL-lactide-co-glycolide) (DL-PLGA) and 0378-5173/96/$15.00 © 1996 Elsevier Science B.V. All rights reserved PH S0378-5173(96)04648-0