Characterization of polymorphic forms of selected active pharmaceutical substance

U sklopu ovog rada prikazane su metode fizikalne karakterizacije i pretraživanja polimorfnih formi aktivne farmaceutske supstance (eng. Active Pharamaceutical Ingredient) te određena stabilnost, higroskopna i morfološka svojstva. Zbog politike tvrtke Pliva Hrvatska d.o.o., kroz rad se ne navodi točan naziv aktivne farmaceutske supstance, već se koristi skraćenica API. Za potrebe fizikalne karakterizacije API-ja primijenjene su rendgenska difrakcijska analiza, diferencijalna pretražna kalorimetrija i termogravimetrijska analiza. Higroskopna svojstva API-ja praćena su njegovim izlaganjem uvjetima relativne vlažnosti na 25 °C te primjenom metode dinamičke sorpcije vlage, dok su za praćenje morfoloških svojstava primijenjene optička mikroskopija i skenirajuća elektronska mikroskopija. Pretraživanje polimorfnih formi ispitivanog API-ja provedeno je njegovim izlaganjem parama otapala kao i izlaganjem otapalima u suspenziji. Također, praćena je i polimorfna stabilnost API-ja tijekom izlaganja različitim stresnim testovima: povišenim temperaturama, povišenim tlačnim silama, mljevenju u kugličnom mlinu i u tarioniku. Fizikalnom karakterizacijom polazne API forme utvrđeno je da je ona stabilna tijekom izlaganja uvjetima relativne vlažnost na sobnoj temperaturi te prilikom izlaganja mehaničkom djelovanju poput tlačnih sila, mljevenja u tarioniku i mehaničkom mlinu. Pretraživanje polimorfnih formi API-ja, provedeno izlaganjem polazne API forme različitim otapalima, rezultiralo je dobivanjem tri nove solvatne forme: 2-metil THF solvata, p-ksilen solvata te n-butanol solvata.This work presents the methods of physical characterization and search of Active Pharmaceutical Ingredient and its polymorphs and determination of its stability, hygroscopic and morphological properties. The exact name of the Active Pharmaceutical Ingredient is not mentioned in the work, due to the policy of Pliva Hrvatska d.o.o.; instead abbreviation API is used. X-Ray diffraction analysis, differential scanning calorimetry and thermogravimetric analysis were applied for physical characterization of the API. The API's hygroscopic properties were monitored by exposing the sample to relative humidity conditions at room temperature and by using the dynamic vapor sorption method. Morphological properties were determined by optical microscopy and scanning electron microscopy. Screening for polymorphic forms of the API was performed by exposing API to solvent's vapor and solvent in suspensions. Also, polymorphic stability of the API was monitored while exposed to various stress tests: exposure to high temperatures and high pressure, milling in ball mill and mortar. Physical characterization of the initial API form indicated its stability during the exposure to relative humidity at room temperature and mechanical actions such as high pressure, milling in mortar and ball mill. Three solvated forms were obtained as a result of the screening process: 2-methyl THF solvate, p-xylene solvate and n-butanol solvate