Release of salbutamol sulphate and ketoprofen enantiomers from matrices containing HPMC and cellulose derivatives.
We studied the release of salbutamol and ketoprofen enantiomers from HPMC K100M matrices containing two types of cellulose derivatives: cellulose tris (3,5-dimethylphenylcarbamate) and cellulose tris (2,3-dichlorophenylcarbamate), chiral excipients used as stationary phases for liquid chromatography. These matrices provided an extended release of both drugs. Ketoprofen release from formulations elaborated with cellulose tris (2,3-dichlorophenylcarbamate) was by anomalous transport, because the value of n (release exponent of the diffusion equation) ranged between 0.60-0.68, whereas for all other formulations the value of exponent n ranged from 0.50-0.54. The drug thus diffuses through the matrix and is released following a quasi-Fickian diffusion mechanism (stereoselective process). The matrices preferentially retained R-salbutamol and S-ketoprofen and cellulose tris (3,5-dimethylphenylcarbamate) showed more capacity of chiral discrimination for both drugs than cellulose tris (2,3-dichlorophenylcarbamate). Moreover, we observed that stereoselectivity is dependent on the amount of chiral excipient in the formulation. Diffusion tests confirmed the chiral interaction between drugs and cellulose derivatives observed in the dissolution assays except for matrices elaborated with ketoprofen and cellulose tris (2,3-dichlorophenylcarbamate), where the low stereoselectivity observed with the matrices is due to the presence of HPMC K100M. We conclude that the inclusion of these cellulose derivatives in HPMC matrices does not result in a relevant stereoselectivity with respect to the two drugs studied.
Solinís
M Angeles
MA
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria, Spain.
de la Cruz
Yaimy
Y
Calvo
Begoña
B
Hernández
Rosa M
RM
Gascón
Alicia R
AR
Goñi
Isabel
I
Gurruchaga
M Dolores
MD
Pedraz
José Luis
JL
D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D002219:Carbamates / Q000008:administration & dosage; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004058:Diffusion; D005079:Excipients / Q000008:administration & dosage; D065347:Hypromellose Derivatives; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry*; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048448:Phenylcarbamates; D012995:Solubility; D013237:Stereoisomerism
D002219:Carbamates; D005079:Excipients; D048448:Phenylcarbamates; C065943:cellulose tris-3,5-dimethylphenyl-carbamate; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; D007660:Ketoprofen; D000420:Albuterol