Matrix type transdermal therapeutic systems of glibenclamide: Formulation, <i>ex vivo</i> and <i>in vivo</i> characterization

Abstract

Matrix type transdermal therapeutic systems (TTS) of glibenclamide were formulated using polymers Eudragit RL 100, ethyl cellulose, PVP K-30, and polyvinyl acetate, and citral was used as the penetration enhancer. The polymer fi lms were formulated with Eudragit RL 100 and PVP K-30 in different ratios and subsequently subjected to ex vivo studies (drug permeation through rat skin) followed by interaction studies, skin irritation studies, accelerated stability analysis, and in vivo studies (determination of blood glucose level in rabbits). The drug content of the formulations was found to be 99.1-99.2%. The cumulative percentages of drug permeated through rat skin from the three selected formulations in 48 h were 95.3%, 98.8%, and 99%, respectively. A plot between cumulative percent of drug permeated and square root of time exhibited linear curves, which suggests the Higuchian matrix mechanism of drug release. The formulation containing Eudragit RL 100 and PVP K-30 showed better improvement in hypoglycemic activity in rabbits (56.2-60.8% reduction in blood glucose level, p < 0.05). There were fewer fluctuations in blood glucose level as compared to oral therapy due to controlled release of the active pharmaceutical ingredient, and no interaction was found between the drug and excipients of the formulation. Accelerated stability analysis showed that the formulation was stable up to 5.5 years, with negligible skin irritation. The formulation precluded severe hypoglycemic reactions (side effect of sulfonylureas) and was effective for management of diabetes mellitus up to 48 h, with a single TTS.

Optimized vinpocetine-loaded vitamin E D-&alpha;-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies

“…43,48 A similar permeation-enhancing effect of citral was reported by Ali et al, who developed glibenclamide transdermal matrix system. 49 The same finding was found with X 3 ; as the percentage of PG (X 3 , plasticizer) increased, the percent of VNP permeated via the rat skin increased. At the same levels of X 1 and X 2 , when the X 3 increased from 1% to 5%, Y 3 increased from 88.15% (F15) to 92.15% (F2), from 66.43% (F3) to 71.85% (F1), and from 64.41% (F6) to 64.69% (F12).…”

Nano-Carrier for Accentuated Transdermal Drug Delivery

“…The model was projected polynomial equation for vesicles particle size is as follow; Y 2 =269.51- 20 The model is significant (F-value=8319.59; p<0.0001), lack of fit (0.02) is not significant and 0.9998 values for predicted R 2 in reasonable agreement with and adjusted R 2 . The X 3 (sonication time) has negative coefficients proved that sonication time has inverse effect on particle size and observed (contour plots which show the effect of different independent variables on particle size (Y 3 ) (Figure 3) that the size of the vesicles significantly increased with increasing concentration of lipid.…”

“…In order to counteract the shortcomings associated with oral therapy of GBD, transdermal delivery system can be developed, which in addition also provides an ease of termination of therapy on manifestation of serious side effects. GBD have already been proven to be effective in management of NIDDM on transdermal administration [20][21][22][23]. For this, the main aim of the study was to develop a novel nano formulation of the model drug i.e.…”

Transdermal delivery of antidiabetic drugs: formulation and delivery strategies

“…Authors attempt to entrap the drug into lipid-based flexible formulation such as ethosomes [47] Ahmed et al investigated the transdermal patches prepared by using chitosan and HPMC that contained self-nanoemulsifying delivery systems of Gm [48] Authors claimed 146.03% increase in relative bioavailability and better blood glucose lowering effect of developed transdermal patch in comparison to oral suspension [49] Limonene was found to be better permeation enhancer for transdermal Gm delivery [50] Thiazolidinedione Biodegradable polymeric nanoparticles of Rg were prepared by using solvent extraction method [64] Ethosomes were prepared that exhibited sustained antidiabetic effect in comparison to oral formulation [65] Transdermal patch comprising HPMC K100 and PVP (1.5%) presented 92.34% drug release [66] Ethosomal carbopol (1%) gel formulation presented in vitro drug release of 89.67% [67] applied to rabbits for 72 h. Authors claimed that the formulation precluded severe hypoglycemic reactions (side-effect of sulfonylureas) and was effective for management of diabetes mellitus for up to 48 h with a single application of the patch [23].…”

“…There were fewer fluctuations in blood glucose level as compared with oral therapy owing to controlled release of the drug. The developed transdermal system was found free of any hazardous skin irritation potential when the patch was Developed transdermal patches showed better control of hyperglycemia over oral microcapsule administration [20] Developed a transdermal patch containing Gb and atenolol to provide greater therapeutic effect for patients having diabetes associated with other noncommunicable diseases, such as hypertension [21] Transdermal system of Gb was developed using polymer such as polymethyl methacrylate and EC [22] Citral was used as the penetration enhancer to improve transdermal Gb delivery [23] Formulation with EC:PVP (3:2) and Eudragit W RL100:Eudragit W RS100 (4:1) was found best among the formulations prepared [24] Ethylene vinyl acetate was found as best release-controlling membrane [25] Best nanoemulsion was obtained by using 15% Labrafac TM and Triacetin, 45% S mix (Tween W 80 and diethylene glycol monoethyl ether) and 4% water [26] Gp Behin et al prepared transdermal film of Gp using chitosan 1.5% w/v [30] Formulation 1 (carbopol gel base + 20% propylene glycol + 15% oleic acid) and formulation 2 (carbopol gel base + Gp-dimethyl-beta-cyclodextrin complex + 15% urea) presented best biological performance [31] Effect of chemical enhancers such as L-menthol, oleic acid and n-octanol on the release of Gp through transdermal matrix patch was studied [32] Prepared the transdermal film using polymer like Eudragit W RLPO and effects of different solvents like acetone, methanol and chloroform on transdermal film formulations were observed [34] Transdermal film containing Eudragit W RL100 and 7.5% oleic acid was found to be the best formulation [35] Authors claimed that two parts of HPMC, two parts of EC and one part of Eudragit W presented best Gp release [36] Gc BCS class II drug MP: 1818C MW: 323.411 Solubility: practically insoluble in water, sparingly soluble in acetone, slightly soluble in ethanol (96%) and freely soluble in dichloromethane Oral bioavailability: $100% t1/2 = 11 h log P = 2.1…”