Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

Abstract

Oral ingestion has been the most convenient and commonly used route of drug administration because of its flexibility and dosage form design (1). In the immediate release (IR) dosage form, there is little or no control of drug release from the dosage form, which often results in constantly changing, unpredictable, and often sub-and supra-the- Extended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media. In vivo study was also performed on six healthy human volunteers and various pharmacokinetic parameters (c max , t max , AUC 0-24 , MRT) and relative bioavailability were calculated. The in vitro and in vivo results were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation. In vitro-in vivo correlation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R = 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation

“…In fact, subcutaneous TR has been demonstrated as an easy alternative to oral, intravenous, or intramuscular routes for postsurgical pain or local infiltrative analgesia. [39][40][41] Several studies have reported the development of new TR formulations such as hydroxypropyl methylcellulose tablets containing semipermeable membranes 42 and ethylcellulose microparticles 43 for oral route. Other examples include chitosan-based adhesives and carbohydrate hydrogels for skin delivery 44,45 and injectable polyhydroxybutyrate microspheres.…”

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™

“…In the present work, an osmotically controlled tablet of tramadol HCl was developed for 24 h; this approach may reduce the requirement of repeated drug administration in a single day and eventually improve patient compliance, whereas, Kumar et al in 2009 developed tramadol HCl osmotic tablets only for 12 h release (Kumar et al, 2009), which may need comparatively frequent drug administration for pain management. To obtain the desirable pharmaceutical parameters within the constraints, factorial design is the widely used DoE to generate sufficient data for formulation optimization based on a predictive model.…”

In vivo performance evaluation and establishment of IVIVC for osmotic pump based extended release formulation of milnacipran HCl

“…The majority of per‐oral CR dosage forms of water soluble drugs fall into the category of matrix, reservoir or osmotic systems. Generally, drug release from matrix and reservoir systems is affected by pH, hydrodynamic conditions and the presence of food in the gastro‐intestinal tract , if the formulation is not well developed. Osmotic systems utilize the principle of osmotic pressure for controlled delivery of drugs .…”