The aim of this study was to prepare injectable depot formulations of Olanzapine using four poly(D,L-lactide-co-glycolide) (PLGA) polymers of varying molecular weight and copolymer composition, and evaluate in vivo performance in rats. In vivo release profiles from the formulations were governed chiefly by polymer molecular weight and to a lesser extent, copolymer composition. Formulations A and B, manufactured using low molecular weight PLGA and administered at 10？mg/kg dose, released drug within 15 days. Formulation C, prepared from intermediate molecular weight PLGA and administered at 20？mg/kg dose, released drug in 30 days, while Formulation D, manufactured using a high molecular weight polymer and administered at 20？mg/kg dose, released drug in 45 days. A simulation of multiple dosing at 7- and 10-day intervals for Formulations A and B revealed that steady state was achieved within 7–21 days and 10–30 days, respectively. Similarly, simulations at 15-day intervals for Formulations C and D indicated that steady state levels were reached during days 15–45. Overall, steady state levels for 7-, 10-, or 15-day dosing ranged between 45 and 65？ng/mL for all the formulations, implying that Olanzapine PLGA microspheres can be tailored to treat patients with varying clinical needs. 1. Introduction Schizophrenia is a debilitating lifelong mental illness that is associated with significant and long-lasting health, social, and financial burdens. Worldwide, it affects more than 24 million of the population with treatment costs amounting to several billion dollars annually [1, 2]. Nonadherence to medications that treat schizophrenia type medical illnesses are generally the primary reason behind the below par results offered by the treatment regimens [3]. Additionally, studies describe a wide range in nonadherence rates (24–74%) among patients [4, 5], resulting in frequent hospitalizations, relapse episodes that not only affect the outcome of the treatment but also contribute to its overall cost. Historically, oral administration of antipsychotics in the form of tablets has been available for the treatment of various schizophrenia type disorders. While being easy to administer, the effectiveness of this type of delivery mechanism faces significant hurdles in most part due to the nature of the illness due to absentmindedness, recoil from ingestion, and so forth. To remedy this, a long-acting injection depot formulation (Haldol Decanoate) was introduced as a treatment option in the 1960s to counter problems facing oral drug delivery [6]. A major advantage to this
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