Process optimization and characterization of poloxamer solid dispersions of a poorly water-soluble drug.
The objective of the present investigation was to improve the dissolution rate of Rofecoxib (RXB), a poorly water-soluble drug by solid dispersion technique using a water-soluble carrier, Poloxamer 188 (PXM). The melting method was used to prepare solid dispersions. A 3(2) full factorial design approach was used for optimization wherein the temperature to which the melt-drug mixture cooled (X(1) ) and the drug-to-polymer ratio (X(2) ) were selected as independent variables and the time required for 90% drug dissolution (t(90)) was selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution of RXB from PXM solid dispersions, a low level of X(1) and a high level of X(2) were suitable. The differential scanning calorimetry and x-ray diffraction studies demonstrated that enhanced dissolution of RXB from solid dispersion might be due to a decrease in the crystallinity of RXB and PXM and dissolution of RXB in molten PXM during solid dispersion preparation. In conclusion, dissolution enhancement of RXB was obtained by preparing its solid dispersions in PXM using melting technique. The use of a factorial design approach helped in identifying the critical factors in the preparation and formulation of solid dispersion.
Shah
Tejal J
TJ
Institute of Pharmacy, Nirma University of Science & Technology, Ahmedabad, Gujarat, India.
Amin
Avani F
AF
Parikh
Jolly R
JR
Parikh
Rajesh H
RH
D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry; D016014:Linear Models; D020442:Poloxamer / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013450:Sulfones / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction
D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D020442:Poloxamer