Development of a Novel Self-Dissolving Microneedle-Assisted Percutaneous Delivery System of Diacerein through Solid Dispersion Gel: Solubility Enhancement, Proof of Anti-inflammatory Activity and Safety

Abstract

Background: Diacerein, an osteoarthiritis drug, experiences slow topical permeation due to limited solubility. Additionally it shows laxative effect due to acid/base hydrolysis of drug in colon. Objective: Diacerein solubility was improved to increase percutaneous drug delivery. Methods: To improve saturation solubility of drug, Diacerein was pre-treated with Polysorbate 80 aqueous solution (1% v/v) to obtain lyophilized powder after wet milling or formulated as solid dispersion using PEG 4000 by fusion method. The lyophilized Diacerein in hydroxypropyl methylcellulose (HPMC 8% w/w) and polyvinyl pyrrolidone (PVP 30% w/w) matrix, with PEG 400 as co-solvent, provided an optimized array. The solid dispersion was loaded in the CMC based gel for subsequent admintration on dissolving microneedle-treated skin. Results: The addition of PEG 400 increased Diacerein loading in microneedles to 390.35±4.28 µg per array. The lyophilized drug displayed amorphous characteristics in the dissolving microneedles as per XRD analysis. SEM photographs showed uniformity in the surface topology of microneedles. The needles showed rapid polymer dissolution within 5 minutes whereas methylene-blue distribution confirmed the formation of microcavities in excised rat skin. The drug-loaded arrays showed better permeation (74.39%) and skin deposition (15.75%) after 24 hours, however, ⁓12% of Diacerein remained in the baseplate. This led to the tailoring of CMC-based gel (3% w/v) containing 0.4% solid dispersion of Diacerein. When compared to untreated skin, the gel improved permeation rate by 2.43 folds through aqueous microchannels generated by dissolving microneedle pre-treatment and allowed 98% drug permeation.. The quasi-Fickian diffusion mechanism was found to drive ex vivo release kinetics, with a shorter lag time (0.88 h) and higher flux (26.65 µg/sq.cm.h). Microneedle-assisted Diacerein gel showed a positive anti-inflammatory effect in the paw edema model and reduced diarrheal episode in comparison to the marketed oral formulation. The gel showed desired characteristics at 5℃±2℃ when tested under accelerated stability conditions. Conclusion: The present study reports for the first time the verification of efficacy and safety to advocate the suitability of Diacerein for percutaneous delivery through dissolving microneedle-treated skin.

Flexible Topical Hydrogel Patch Loaded with Antimicrobial Drug for Accelerated Wound Healing

“…The in vitro release tests were conducted at pH 5.5 for normal skin and pH 6.5 and 7.4 for injured skin [39]. Figure 6A shows that with an increase in HEC concentration, the drug release pattern increased from HECA-1 to HECA-3.…”

“…The aluminum stub was then positioned in the vacuum chamber of the microscope and morphologically assessed using an electron beam. A photomicrograph examined under a microscope was used for the morphological characterization of the topical patch [39].…”

“…For TGA analysis, a 0.5-5 mg sample was placed in an open platinum 100 µL pan that was attached to a microbalance and heated to 20-600 • C under dry nitrogen. For DSC, the sample was placed into an aluminum pan and heated with nitrogen gas at a rate of 20 • C/min [39].…”

Diacerein Loaded Novasome for Transdermal Delivery: Prepartion , In-Vitro Characterization and Factors Affecting Formulation

“…Several attempts have been investigated to replace oral administration of Diacerein (7,8) . Dermal delivery seems to be an attractive approach.…”