Estudo de pré-formulação, desenvolvimento farmacotécnico e caracterização de formas farmacêuticas sólidas da olanzapina
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2010-06-21
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Universidade Federal de Goiás
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.
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PERES FILHO, Marco Júnio. Study of pre-formulation, pharmaceutical development and
characterization of solid dosage forms of olanzapine. 2010. 138 f. Dissertação (Mestrado em Ciências da Saúde - Farmácia) - Universidade Federal de Goiás, Goiânia, 2010.