Polymeric Matrix System for Prolonged Delivery of Tramadol Hydrochloride, Part I: Physicochemical Evaluation

Abstract

Abstract. Management of moderate or severe chronic pain conditions is the burden of clinicians dealing with patients trying to improve their quality of life and diminish their suffering. Although not a new opioid, tramadol has been recently rediscovered and widely used; this may be due to its favorable chronic safety and dependence profiles together with its high potency. Tramadol is a centrally acting analgesic with half-life of~6 h; therefore, it requires frequent dosing. It is freely soluble in water; hence, judicious selection of retarding formulations is necessary. The current study is focused on the innovation of a novel, simple, monolayer, easy-to-use, cost-effective, and aesthetically acceptable bioadhesive transdermal delivery system overcoming the defects of the conventional "patch" as carrier system for tramadol, ensuring its adequate delivery, along with the physicochemical evaluation of the designed formulations. Monolithic tramadol matrix films of chitosan, different types of Eudragit ® , and binary mixtures of both were prepared. As a single-polymer film, chitosan film showed best properties except for somewhat high moisture uptake capacity, insufficient strength and rapid release, and permeation. Polymer blends were monitored in order to optimize both properties and performance. Promising results were obtained, with chitosan-Eudragit ® NE30D (1:1) film showing the most desirable combined, sufficiently rapid as well as prolonged release and permeation profiles along with satisfactory organoleptic and physicochemical properties.

Development and evaluation of long-acting epidural “smart” thermoreversible injection loaded with spray-dried polymeric nanospheres using experimental design

“…This is further supported by the fact that the combination of polymer hydration, drug dissolution and polymer erosion determine the drug release from matrix system. It is well known that water-soluble drugs are released primarily by diffusion of dissolved drug molecules across the matrix layers (Ammar et al, 2009a).…”

“…Sustaining the release of Tramadol HCl, being a freely soluble drug with a short half-life, was the aim of many pharmaceutical studies (Ammar et al, 2009a(Ammar et al, , 2009bKamel et al, 2012); however, most of the researchers were focused on the oral route and no one had studied the epidural Tramadol delivery. Although Salman et al (2003) have published a manuscript concerned with the encapsulation of the drug into only one formula consisting of polyhydroxybutyrate microspheres for epidural analgesia, however, this manuscript had not presented the full in vitro investigation comprising formulation preparation, characterization, comparison and evaluation.…”

Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems

“…Polymeric filmforming systems (FFS), created in situ after administration, offer a more efficient and patientfriendly topical formulation with the potential to increase and/or sustain drug delivery and permit less frequent dosing [3][4][5][6][7]. Additionally, incorporation of plasticisers into FFS has been demonstrated to increase the in vitro release of incorporated drugs [8][9][10][11]. Given that increased BMV release and skin uptake with increasing plasticiser lipophilicity and higher MCT concentrations had been observed in earlier work [7,12], this investigation primarily focused on the effect of the lipidic medium-chain triglyceride (MCT), which is a well-known excipient in dermatologic formulations.…”

In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic

“…Transdermal drug delivery, a non‐invasive drug administration route, offers the potential benefits of simplicity, efficacy and patient acceptance by maintaining a constant blood drug concentration for an extended period of time with acceptable interpatient variations [6–8] . In addition, the transdermal delivery system can decrease the possible abuse and addiction potential of tramadol [9,10] by avoiding peak and trough plasma concentrations and by reducing the total amount of medication input [11,12] . Hence, a transdermal delivery system is a desirable alternative administration route for tramadol hydrochloride for patients with chronic pain.…”