Development of Meloxicam Oral Lyophilisates: Role of Thermal Analysis and Complementary Techniques

Abstract

The purpose of this study was to highlight the way in which thermoanalytical and complementary techniques can guide the development of meloxicam oral lyophilisates both in the preformulation and formulation stages, as well as for the final products characterization. Thermoanalytical methods (differential scanning calorimetry -DSC, thermogravimetry -TGA) and complementary methods (Fourier transform infrared -FTIR, X-Ray powder diffraction -XRPD, scanning electron microscopy -SEM) were applied in order to obtain a complete set of data. In the preformulation stage, the compatibility between meloxicam and excipients was assessed. DSC results showed the compatibility between meloxicam and excipients. Tg' measurement in the frozen state led to the addition of an annealing step at -25°C into the freezing stage, to facilitate complete crystallization and end-product integrity. The designed lyophilization cycle yielded good cake appearance. The DSC, XRPD analysis as well as SEM morphology studies, performed in the final stage, evidenced that the meloxicam freezedried products were partially crystalline. By the TGA analysis the moisture content was evaluated in accordance or close to the recommended limits. In conclusion, thermoanalytical techniques are well suited for the design of freeze-drying process, in order to obtain good quality oral lyophilisates. RezumatScopul acestui studiu a fost acela de a evidenția felul în care tehnicile de analiză termică și unele tehnici complementare pot ghida procesul de dezvoltare a liofilizatelor orale cu meloxicam, atât în etapele de preformulare și formulare, cât și pentru caracterizarea produselor finale. Metodele termice de analiză (analiza calorimetrică diferențială -DSC, analiza termogravimetrică -TGA) și cele complementare (spectroscopia în infraroșu cu transformantă Fourier -FTIR, difracția de raze X -XRPD, microscopia electronică de baleiaj -SEM) au fost aplicate pentru obținerea unui set complet de date. Astfel, în etapa de preformulare a fost studiată compatibilitatea dintre meloxicam și excipienții aleși. Rezultatele DSC au arătat existența compatibilității dintre aceștia. Determinarea Tg' în faza de înghețare a liofilizării a dus la includerea unui tratament termic la -25°C, cu scopul de a asigura structura cristalină și integritatea produsului final. Ciclul de liofilizare astfel optimizat a dus la obținerea unor liofilizate orale corespunzătoare vizual. Designul ciclului de liofilizare a fost realizat pornind de la datele DSC înregistrate, care au evidențiat temperaturile critice asociate diferitelor caracteristici fizice ale materialelor în starea înghețată. Analizele DSC, XRPD precum și studiile de morfologie SEM efectuate în etapa finală, au evidențiat faptul că liofilizatele orale cu meloxicam obținute au fost parțial cristaline. Prin metoda TGA s-a determinat conținutul acestora în umiditate, rezultatele înregistrate fiind în concordanță sau aproape de limitele recomandate. În concluzie, tehnicile de analiză termică sunt foarte potrivite pentru designul procesului de...

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