On the preparation of opioid-loaded cutaneous patches

Purpose - The aim of the present study was i) to evaluate the feasibility of opioid-loaded cutaneous patches made of methacrylic-based adhesive matrix and ii) to rationalize the selection of the best compounds to be loaded into patches intended to act locally for assuring local skin analgesia. Methods - Dihydromorphine (DM), oxymorphone (OM), hydromorphone (HM), dihydrocodeine (DC), oxycodone (OC) and hydrocodone (HC) were used as free bases and loaded (1% w/w) in cutaneous patches, made of Eudragit NE 40® and triacetin (50/50% w/w of dried weight). Patches were prepared by casting using a laboratory-coating unit Mathis LTE-S(M) (Mathis, CH) and they were characterized in terms of drug release rate (Kr), permeation flux (J) and drug amount retained in the HE (Qret). The dissolution studies were performed using an adapted disk assembly method. In vitro permeation and retention studies were carried out with the Franz diffusion cells using human epidermis (HE) as model membrane. Results - The compounds with hydroxyl group in position 14 (i.e., OM, OC) resulted in the highest Kr-values (p=0.02). Furthermore, the codeine derivatives exhibited higher Qret values than the morphine ones, except for HM. Among all the opioid derivatives investigated, no statistical differences were observed in terms of J, with the only exception of DM (p=0.0177) that showed the highest J-value. Table 1. Kr, J, Qret values and the Qret normalized by μ-receptor binding potency [1] of the opioid-loaded patches (Mean ± St.Dev.; n=3). Form. Kr (h-0,5) Qret (μg/mg) J (μg/cm2h) Normalized Qret DM 0.10±0.01 0.27±0.09 0.31±0.16 1.10*10-1 OM 0.11±0.01 0.29±0.09 0.07±0.02 3.00*10-1 HM 0.09±0.03 1.38±0.43 0.16±0.09 4.93 DC 0.07±0.01 1.14±0.20 0.09±0.03 3.51*10-3 OC 0.10±0.01 1.40±0.24 0.07±0.01 8.00*10-2 HC 0.08±0.02 1.32±0.18 0.01±0.00 1.20*10-1 Aiming to rationalize the selection of suitable candidates for local analgesia by application of opioid-loaded cutaneous patch, the major features to be considered are both a high tendency to be retained in HE and a high binding affinity for the opioid receptors. In the light of this consideration, the HM was selected as the most promising candidate from the comparison of the normalized Qret. Conclusions - The methacrylic matrix resulted effective in loading and controlling the release profiles of six morphine derivatives as well as in promoting the drug retention in the HE. Furthermore, the experimental studies confirmed the selection of HM for the design of a cutaneous patch intended to assure local analgesia. References 1. Musazzi, U.M. et al. Int. J. Pharm. (2015) 489: 177-185.