Microcapsules and Transdermal Patch: A Comparative Approach for Improved Delivery of Antidiabetic Drug

Abstract

Abstract. Glibenclamide (GL)-loaded microcapsules (MC) and transdermal patches (TDP) were formulated and in vitro and in vivo parameters compared to find out the best route of drug administration. The formulation TDP1 having a drug-polymer ratio 1:1 showed comparatively higher GL release and better permeation across mice skin (p<0.05). From the comparative study, it was concluded that the transdermal system of GL produced better improvement compared to oral microcapsule administration (p<0.05). The transdermal system exhibited comparatively slow and continuous supply of GL at a desired rate to systemic circulation avoiding metabolism, which improved day-to-day glycemic control in diabetic subjects. Transdermal system of GL exhibited better control of hyperglycemia and prolonged plasma half-life by transdermal systems (9.6±1.2 h) in comparison with oral microcapsule (5.84±2.1 h), indicating that the drug, when administered by transdermal systems, will remain in the body for a longer period. From the glucose tolerance test, transdermal route effectively maintained the normoglycemic levels in contrast to the oral group (MC1), which produced remarkable hypoglycemia ranging from −12.6±2.1% to −18±2.3%. The significantly high (p<0.05) area under the curve values observed with transdermal system (1,346.2±92.3 ng ml −1 h −1 ) also indicate increased bioavailability of the drug from these systems compared to the oral route (829.8±76.4 ng ml −1 h −1 ).

The Sur1-Trpm4 Channel in Spinal Cord Injury

“…From a pharmacokinetic perspective, cutaneous delivery of glibenclamide is highly effective for maintaining steady plasma levels, is superior to enteral administration, and appears to be equivalent to intravenous (IV) administration [67]. Constant subcutaneous infusion of glibenclamide was used in the preclinical studies as a convenient alternative to constant IV infusion, as is used with injectable glibenclamide (RP-1127) in clinical trials for other CNS indications (ClinicalTrials.gov identifiers: NCT01454154; NCT01268683; NCT01794182).…”

Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

“…From a pharmacokinetic perspective, cutaneous delivery of glibenclamide is highly effective for maintaining steady plasma levels, is superior to enteral administration and appears to be equivalent to intravenous (IV) administration. 23 Constant subcutaneous infusion of glibenclamide was used in the preclinical studies as a convenient alternative to constant IV infusion, as is used with injectable glibenclamide (RP-1127) in clinical trials for other CNS indications (ClinicalTrials.gov identifiers: NCT01454154; NCT01268683; NCT01794182). In the animal studies, no clinically relevant hypoglycemia or other toxicity has been detected with infusions of 200 ng h À1 4,12,13 or 400 ng h À1 .…”

Transdermal delivery of antidiabetic drugs: formulation and delivery strategies

“…The Gb transdermal system demonstrated better control of hyperglycemia and prolonged plasma half-life in comparison with oral microcapsules; indicating that the drug remains in the body for a longer period with transdermal administration. Additionally, significantly high area under the curve values of Gb were observed after transdermal application compared with the oral route [20].…”

“…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…”