Controlled release of bupivacaine HCl through microchannels of biodegradable drug delivery device

Local and prolonged delivery of local analgesics is much desired for post-operative pain management. For delivery of local analgesics at a constant rate over couple of days, a microfluidic device comprised of a drug reservoir and microchannels for drug release was developed using a biodegradable polymer, 85/15 poly(lactic-co-glycolic acid). Unlike conventional methods relying on material property, this device enables convenient modulation of the release speed of drugs by a simple change of the channel geometry such as the length and cross-sectional area. Bupivacaine was selected as our model local analgesic drug and its diffusional transport through microchannels was studied using the microfluidic devices. However, since the salt form of bupivacaine, bupivacaine hydrochloride, has pH-dependent solubility, its precipitation in microchannels had an adverse impact on the release performance of the microfluidic drug delivery devices. Thus, in this investigation, the diffusional transport and precipitation of bupivacaine hydrochloride in microfluidic channels were studied using in vitro release experiments and optical analysis. Furthermore, a concept of co-delivery of bupivacaine hydrochloride together with acidic additives was demonstrated to achieve a zero-order delivery of bupivacaine hydrochloride without the clogging of microchannels by its precipitation.