(W0930-10-56) Ethyl Cellulose Coated Polymeric Microneedles for the Controlled Delivery of Drugs

Purpose: The purpose of the project was to explore the possibility of fabrication of polymer coated polymeric microneedles for controlled delivery of APIs into the tissues. This approach would deliver only the drug in a controlled release manner without allowing the excipients to dump into the tissue unlike in the uncoated immediate release dissolvable microneedles.

Methods: Polymer coated polymeric (PCP) microneedles were fabricated using the mold casting technique. PDMS (Poly Dimethyl Siloxane) molds array composed of 6 x 6 microneedles were used to cast the microneedles. PVP K30 (20% w/v) solution was prepared in distilled water and used as a casting solution. Fabricated microneedles were coated with ethyl cellulose (Ashland, USA) solution (1-4%w/v prepared in toluene) by dip-and-spin coating technique. Toluene with 4%w/v ethyl cellulose was found to answer the hypothesis of the study. FITC-Dextran, FITC-Albumin, voriconazole, and lidocaine hydrochloride loaded PCP microneedles were prepared to study potential transdermal and ocular applications. Dermal delivery of lidocaine loaded PCP microneedles was studied by conducting in vitro permeation studies across the porcine skin and intravitreal delivery of voriconazole was studied using excised porcine eyes. Analysis of FITC-dextran and FITC-albumin was carried out using a fluorescence spectrophotometer and all the other actives were analyzed on an HPLC-UV system. Characterization tests of the fabricated PCP microneedles like microscopy, mechanical strength analysis and to test the defects in the coating after exposure to the release medium were performed.

Results: It is clear from the SEM images that the coating was uniform all over the microneedles (Figure 1a b & c). To assess the coating of the PCP microneedles, FITC albumin was incorporated into the microneedles and dipped in the PBS buffer for 6 hours. The release studies in PBS buffer for 6 hours revealed that there was absolutely no leaching of the fluorescein albumin in the receiver indicating the intactness of the coat. The release of FITC dextran from uncoated microneedle was instantaneous with almost 100% release found in the first 10 mins, from both 1% and 2% FITC dextran loaded microneedles (n=3). Whereas PCP microneedles led to a slow and controlled release of the drug for up to 2 hours. In the case of PCP microneedles, there was only 34.54±1.551% and 28.710±0.747% release of FITC dextran observed in the first 10 mins from 1% and 2% FITC dextran loaded PCP microneedles respectively (Figure-2). Lidocaine hydrochloride was delivered transdermally using PCP microneedles. Lidocaine hydrochloride is a local anesthetic and a pain modulator. Prolonged delivery of drug could led to a longer sustained pain modulation effect in case of management of chronic pain associated with neurological disorders and injuries. The amount of lidocaine in the microneedles was 498± 22µg. The release of Lidocaine hydrochloride from uncoated microneedles was instantaneous. On the other hand, the PCP microneedles led to a slow and controlled release and permeation of the drug up to 8 hours, with 88 ±12 µg permeated after the first hour and 466.87± 12µg permeated after 8 hours. (Figure 3a). The amount of voriconazole in the microneedles was 218.35±59.45 µg. When delivered using PCP microneedles, there was absolutely no polymer disintegration in the vitreous humor and the PCP microneedles were recovered intact after 6 hours (Figure-1d). The total amount of drug found in the vitreous humor, one hour after application of uncoated microneedles was about 65.58 ±11.25 µg. Whereas in the case of PCP microneedles the cumulative amount of drug in the vitreous humor increased incrementally up to 6 hours, with 19.59±5.1 drug detected at 1 hour and gradually increased to 60.24±7.4 after 6 hours (Figure-3b), demonstrating the feasibility of infusing the drug in a controlled manner into the vitreous humor.

Conclusion: The results suggested that the PCP microneedles provide many advantages over soluble microneedles such as it could retard the release of the actives significantly compared to soluble microneedles and do not let the polymer and other components used to manufacture the microneedles deposit in the tissue.

Acknowledgements: The author is thankful to the BASF and Ashland for providing the polymers to carry out this research. The author is also thankful to the University of Mississippi's Microscopic and Imaging Centre (SEM Core) for performing the scanning electron microscopy analyses.


Figure 1: SEM images of a) Uncoated Microneedle b) PCP Microneedle c) Microneedle intentionally plugged from the base to differentiate the uniformity and texture of the coating d) single PCP microneedle after exposure to the buffer (PBS) for 6 hours. One side of the microneedle was chopped using a fine blade to be able to get the distinction between the core and the coat.


Figure 2: Release pattern from uncoated Microneedle and PCP microneedle loaded with different percentages of FITC-dextran


Figure 3: a) Permeation of lidocaine hydrochloride across porcine skin from uncoated microneedles prepared with PVP-K30 (20%w/v casting solution) and PCP microneedles coated with ethyl cellulose N7 (4%w/v coating solution) (n=6±sd). b) Amount of voriconazole in the porcine vitreous humor at different points of time after application of microneedle array (n=6±sd) from uncoated microneedles prepared with PVP-k30 (20%w/v casting solution) and PCP microneedles coated with ethyl cellulose N7 (4%w/v coating solution).