The use of in situ near infrared spectroscopy to provide mechanistic insights into gel layer development in HPMC hydrophilic matrices.

In this study, near infrared (NIR) spectroscopy has been used to track the spatial and temporal movement of a model drug (Compound A) while monitoring in situ the gel layer development in hydrophilic matrices based on hydroxypropyl methylcellulose (HPMC). To validate the NIR experimental set-up, Compound A was formulated in "slow" and "fast" drug releasing formulations with high (56% w/w) and low (18% w/w) levels of HPMC K100M, respectively. NIR microscopy was used to (i) define the extent of HPMC pseudo-gel swelling, (ii) elucidate the movement of the polymer swelling front and (iii) track movement of the drug through the gel layer. Dissolution testing (USP I) allowed correlation of mechanistic details ascertained using NIR with the rate and extent of drug release. Several critical differences were observable between "fast" and "slow" formulations. In the "fast" formulation, HPMC swelling front movement occurred at a slower rate and to a lesser extent compared to drug release, suggestive of inadequate gel layer formation and a partial loss of extended release characteristics. In contrast, the "slow" formulation exhibited a similar rate of HPMC swelling front movement compared to drug release, suggesting a release mechanism predominately controlled by polymer erosion, supported by an apparent zero order drug dissolution curve in USP I. In conclusion, the study suggests the potential future value of using NIR in situ to elucidate mechanistic insights in drug release rate from pharmaceutical formulations.