Study of pre-formulation, pharmaceutical development and characterization of solid dosage forms of olanzapine / Estudo de pré-formulação, desenvolvimento farmacotécnico e caracterização de formas farmacêuticas sólidas da olanzapina

AUTOR(ES)
DATA DE PUBLICAÇÃO

2010

RESUMO

Among manufacturing processes available, direct compression is indicated for OLZ because this drug is moisture sensitive. Before drug developement, preformulation investigations involving physical and chemical properties of drug and excipient combined and separated must be performed. Thus, drug solubility profile, thermal analysis techniques, mainly DSC and TG, and X rays graphics are used to verify drug behavior. The objective of this work was preformulation study of OLZ, drug development and characterization of OLZ tablets to accomplish pharmaceutical equivalence. DSC and TG tests were performed, as well as X rays diffraction and solubility test in different media. Media used in solubility assay were: water; HCl 0,1 mol/L; and USP buffers pH 2.5; pH 4.5; pH 6.8 and pH 7.4. This test duration was 48h. OLZ showed to be more soluble in acidic pH, HCl medium, in which it reached the concentration of 20,62 mg/mL, without saturation. In buffers pH 2.5 and 4.5 saturation solubility was 2,06 mg/mL and 5,19 mg/mL, respectively; in pH 6.8 and pH 7.4 OLZ reached only 221,45 μg/mL and 79,06 μg/mL, respectively. Concentration of OLZ in water was even lower, 48,87 μg/mL. OLZ did not show incompatibility evidence when mixed with corn starch, croscarmellose, crospovidone, dicalcium phosphate anhydrous and dihydrate, magnesium stearate, microcrystalline cellulose PH-101 and PH-102, sodium lauryl sulfate and titanium dioxide. There was solid state interaction with ethylcellulose and opadry YS-1- 7006, and incompatibility with silicon dioxide and PEG 4000. There was also evidence of interaction in DSC and TG with both types of lactose tested, 22AN e monohydrate. Lactose monohydrate sample did not confirm interaction by X rays diffraction analysis. However, lactose is not the best choice of diluent to dosage forms containing OLZ, due to indications of Maillard reaction occurrence between referred substances. Olanzapine tablets were obtained, with 2,5 mg of dosage, by direct compression process, due to drug moisture sensitiveness. When microcrystalline cellulose PH-102 was used in formulations as major diluent, physical specifications were reached. It was used together with dicalcium phosphate anhydrous to improve formulation flowability. Coating suspension formulation contained opadry YS-1- 7006, methocel K4MPR and titanium dioxide in total concentration of 10%. Though this film coating appropriate drug release profile was reached, as well as pharmaceutical equivalence.

ASSUNTO(S)

olanzapina dsc tg solubilidade comprimidos farmacia 1.olanzapina 2.calorimetria exploratória diferencial 3.solubilidade olanzapine dsc tg solubility tablets

ACESSO AO ARTIGO

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