Development of matrix controlled transdermal delivery systems of pentazocine: In vitro/in vivo performance

Abstract

Transdermal drug delivery system is being extensively investigated as a viable alternative to drug delivery with improved bioavailability. It offers many advantages over conventional administration such as enhanced efficacy, increased safety, and greater convenience and improved patient compliance. Transdermal route permits the use of a relatively potent drug with minimal risk of systemic toxicity and avoids gastrointestinal degradation and hepatic first-pass metabolism (1-3). A number of therapeutic agents, including antihypertensive, antianginal, antihistaminic, anti-inflammatory, analgesic, The present study aimed to develop hydroxypropyl methylcellulose based transdermal delivery of pentazocine.In formulations containing lower proportions of polymer, the drug released followed the Higuchi kinetics while, with an increase in polymer content, it followed the zero-order release kinetics. Release exponent (n) values imply that the release of pentazocine from matrices was non-Fickian. FT-IR, DSC and XRD studies indicated no interaction between drug and polymer. The in vitro dissolution rate constant, dissolution half-life and pharmacokinetic parameters (C max , t max , AUC (s) , t 1/2, K el , and MRT) were evaluated statistically by two-way ANOVA. A significant difference was observed between but not within the tested products. Statistically, a good correlation was found between per cent of drug absorbed from patches vs. C max and AUC (s) . A good correlation was also observed when per cent drug released was correlated with the blood drug concentration obtained at the same time point. The results of this study indicate that the polymeric matrix films of pentazocine hold potential for transdermal drug delivery.Keywords: pentazocine, transdermal drug delivery, Cygnus' sandwich patch holder, in vitro characterization, in vivo evaluation * Correspondence; e-mail: prpverma275730@yahoo.com Unauthenticated Download Date | 8/28/18 7:56 PM and anti-arthritic drugs, are being investigated and developed for the transdermal therapeutic system either for academic research or for commercial purposes (3, 4). The present work is aimed at developing a matrix-dispersion type transdermal drug delivery of pentazocine.Pentazocine (PTZ), a benzomorphan derivative, is an opioid analgesic that has mixed opioid agonist and antagonist actions. It is considered to be a partial agonist or weak antagonist at the m-receptor and a k-receptor agonist. Pentazocine is used for relief of moderate to severe pain. Oral administration of PTZ has the disadvantage of low bioavailability (about 18-22 %) due to extensive first-pass metabolism (5-7). In addition, PTZ has a short half-life of 2-4 h and requires frequent dosing in order to maintain the optimal therapeutic concentration. Repeated injections over long periods may cause fibrotic changes in the skin and muscular tissue. Low molecular mass (285.4), suitable pK a values of 8.5 and 10, log P (octanol/phosphate buffer pH 7.4) of 2.0 and low oral bioavailability provide a rationale for developing a...

Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization

“…However, the oral administration of PTZ is associated with some drawbacks in terms of poor bioavailability (18-20%), short half-life (2-3 hours) and extensive first pass metabolism that required multiple dosing regimens to maintain the desired therapeutic levels. Interestingly, some of the physicochemical properties of the PTZ, such as Low molecular mass (285.4) and low oral bioavailability, suitable pKa values of 8.5 and 10 and log P of 2.0 make it an ideal candidate to formulate in a novel sustained release DDS such as microsphere which enhanced the therapeutic outcomes of the therapy by using PTZ [10,12,13].…”

Effect of permeation enhancers on in vitro release and transdermal delivery of lamotrigine from Eudragit®RS100 polymer matrix-type drug in adhesive patches

“…No overlapping or merging of spectral peak was observed indicating that there is no interaction between polymer, enhancer and drug. The FTIR drug-excipient compatibility study of matrix-type transdermal patches is extensively reported in the literature (Mukherjee et al 2005 ; Prasad Verma and Chandak 2009 ; Rajabalaya 2010 ; Rajan et al 2009 ; Shinde et al 2008 ; Ubaidulla et al 2007 ). Eudragit RS used as matrix-forming agent is found compatible with most of the drugs (Wade and Weller 1994 ).…”

Ultra-flexible nanocarriers for enhanced topical delivery of a highly lipophilic antioxidative molecule for skin cancer chemoprevention

“…The cumulative drug release plots were fitted to the mathematical models for zero-order (r 0 ), first-order (r 1 ) and Higuchi-type (r H ) release kinetics in accordance with the methods of Verma et al [34] and Costa et al [35]. The slopes of the fitted plots were used to estimate the release rates.…”

“…The authors showed that when the polymer relaxation rate was similar to that of the diffusion, the anomalous or non-Fickian diffusion pattern of drug release was observed [34]. However, there was reduced deposition of DIM-D within the skin layers observed with increase in polymer concentration, suggesting that there may be other factors playing roles in the permeation of the drug, which is highly lipophilic such as polymer relaxation with time, polymer interaction with the drug and drug permeation with time.…”