Abstract
PURPOSE
A mathematical model is described for the prediction of the relative change in drug release rate as a function of formulation composition for HPMC-based extended-release (ER) tablets of adinazolam mesylate and alprazolam.
METHODS
The model is based on the equation derived by Higuchi for the diffusional release of soluble drugs from polymeric matrices and on our recent measurements of the concentration dependency of adinazolam diffusivity in dilute HPMC gels and solutions. The assumptions made in applying the model include (i) that diffusion is the sole mechanism of drug release (i.e. swelling kinetics are ignored), and (ii) that the surface area-to-volume ratio and concentrations of adinazolam, lactose and HPMC in the gel layer are proportional to that of the dry tablet.
RESULTS
Reasonable correlations were obtained between the experimental drug release rate ratios and the predicted drug release rate ratios for ER adinazolam mesylate (R2 = 0.82) and low-dose (0.5 mg) ER alprazolam tablets (R2 = 0.87). The predictive power for a 6-fold higher dose of ER alprazolam tablets was not as good (R2 = 0.52).
CONCLUSIONS
These results are consistent with previous knowledge of the release mechanisms of these formulations. ER adinazolam mesylate and ER alprazolam 0.5 mg exhibit primarily a diffusion controlled release mechanism, while ER alprazolam 3 mg deviates from pure diffusional release. The limitations of the model are discussed and point to the need for continued study of the swelling kinetics of matrix ER systems.
TY - JOUR
T1 - Diffusion in HPMC gels. II. Prediction of drug release rates from hydrophilic matrix extended-release dosage forms.
AU - Gao,P,
AU - Nixon,P R,
AU - Skoug,J W,
PY - 1995/7/1/pubmed
PY - 1995/7/1/medline
PY - 1995/7/1/entrez
SP - 965
EP - 71
JF - Pharmaceutical research
JO - Pharm Res
VL - 12
IS - 7
N2 - PURPOSE: A mathematical model is described for the prediction of the relative change in drug release rate as a function of formulation composition for HPMC-based extended-release (ER) tablets of adinazolam mesylate and alprazolam. METHODS: The model is based on the equation derived by Higuchi for the diffusional release of soluble drugs from polymeric matrices and on our recent measurements of the concentration dependency of adinazolam diffusivity in dilute HPMC gels and solutions. The assumptions made in applying the model include (i) that diffusion is the sole mechanism of drug release (i.e. swelling kinetics are ignored), and (ii) that the surface area-to-volume ratio and concentrations of adinazolam, lactose and HPMC in the gel layer are proportional to that of the dry tablet. RESULTS: Reasonable correlations were obtained between the experimental drug release rate ratios and the predicted drug release rate ratios for ER adinazolam mesylate (R2 = 0.82) and low-dose (0.5 mg) ER alprazolam tablets (R2 = 0.87). The predictive power for a 6-fold higher dose of ER alprazolam tablets was not as good (R2 = 0.52). CONCLUSIONS: These results are consistent with previous knowledge of the release mechanisms of these formulations. ER adinazolam mesylate and ER alprazolam 0.5 mg exhibit primarily a diffusion controlled release mechanism, while ER alprazolam 3 mg deviates from pure diffusional release. The limitations of the model are discussed and point to the need for continued study of the swelling kinetics of matrix ER systems.
SN - 0724-8741
UR - https://www.unboundmedicine.com/medline/citation/7494816/Diffusion_in_HPMC_gels__II__Prediction_of_drug_release_rates_from_hydrophilic_matrix_extended_release_dosage_forms_
L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=7494816.ui
DB - PRIME
DP - Unbound Medicine
ER -
