Thermal processing of a poorly water-soluble drug substance exhibiting a high melting point: the utility of KinetiSol® Dispersing.
Int J Pharm
; 419(1-2): 222-30, 2011 Oct 31.
Article
em En
| MEDLINE
| ID: mdl-21864663
ABSTRACT
Poorly water-soluble drug substances that exhibit high melting points are often difficult to successfully process by fusion-based techniques. The purpose of this study was to identify a suitable polymer system for meloxicam (MLX), a high melting point class II BCS compound, and investigate thermal processing techniques for the preparation of chemically stable single phase solid dispersions. Thermal and solution based screening techniques were utilized to screen hydrophilic polymers suitable for immediate release formulations. Results of the screening studies demonstrated that Soluplus(®)(SOL) provided the highest degree of miscibility and solubility enhancement. A hot-melt extrusion feasibility study demonstrated that high temperatures and extended residence times were required in order to render compositions amorphous, causing significant degradation of MLX. A design of experiments (DOE) was conducted on the KinetiSol(®) Dispersing (KSD) process to evaluate the effect of processing conditions on the chemical stability and amorphous character of MLX. The study demonstrated that ejection temperature significantly impacted MLX stability. All samples prepared by KSD were substantially amorphous. Dissolution analysis of the KSD processed solid dispersions showed increased dissolution rates and extent of supersaturation over the marketed generic MLX tablets.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Tiazinas
/
Tiazóis
/
Portadores de Fármacos
/
Anti-Inflamatórios não Esteroides
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos