Acyclovir is an antiviral drug that is frequently prescribed for the herpes virus. However, the drug requires frequent dosing due to limited bioavailability (10–26.7%). The rationale of the present study was to develop a self-dissolving microneedle system for local and systemic delivery of acyclovir using a topical lyophilized wafer on microneedle-treated skin to provide the drug at the site of infection. The microneedles prepared with hydroxypropyl methylcellulose (HPMC) (8% w/w) or HPMC (8% w/w)-polyvinyl pyrrolidone (PVP) (30% w/w) penetrated excised rat skin, showing sufficient mechanical strength and rapid polymer dissolution. The topical wafer was prepared with acyclovir (40% w/w; equivalent to 200 mg of drug), gelatin (10% w/w), mannitol (5% w/w), and sodium chloride (5% w/w). The uniform distribution of acyclovir within the wafer in an amorphous form was confirmed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). No polymer–drug interaction was evident in the lyophilized wafer as per Fourier transform infrared spectroscopy (FTIR) analysis. The wafer showed a sufficiently porous structure for rapid hydration as per scanning electron microscopy (SEM) analysis. During ex-vivo analysis, the skin was pre-treated with a self-dissolving microneedle array for 5 minutes, and the wafer was placed on this microporated-skin. Topical wafer provided ∼7–11 times higher skin concentration than the ID99 reported with a lower lag-time. Based on in-vivo testing, ∼2.58 µg/ml of Cmax was achieved in rabbit plasma during 24 hours’ study. Our findings suggest that the self-dissolving microneedle-assisted topical wafer, proposed for the first time, would be efficacious against the infection residing in the skin layer and for systemic therapy.

The delivery of drugs, via different layers of skin, is challenging because it acts as a natural barrier and exerts hindrance against molecules to permeate into or through it. To overcome such obstacles, different noninvasive methods, like vehicle-drug interaction, modifications of the horny layer and nanoparticles have been suggested. The aim of the present review is to highlight some of the non-invasive methods for topical, diadermal and transdermal delivery of drugs. Special emphasis has been made on the information available in numerous research articles that put efforts in overcoming obstacles associated with barrier functions imposed by various layers of skin. Advances have been made in improving patient compliance that tends to avoid hitches involved in oral administration. Of particular interest is the use of lipid-based vesicles and nanoparticles for dermatological applications. These particulate systems can effectively interact and penetrate into the stratum corneum via lipid exchange and get distributed in epidermis and dermis. They also have the tendency to exert a systemic effect by facilitating the absorption of an active moiety into general circulation.

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.

: Nanosized particles, with a size of less than 100 nm, have a wide variety of applications in various fields of nanotechnology and biotechnology, especially in the pharmaceutical industry. Metal nanoparticles [MNPs] have been synthesized by different chemical and physical procedures. Still, the biological approach or green synthesis [phytosynthesis] is considered as a preferred method due to eco-friendliness, nontoxicity, and cost-effective production. Various plants and plant extracts have been used for the green synthesis of MNPs, including biofabrication of noble metals, metal oxides, and bimetallic combinations. Biomolecules and metabolites present in plant extract cause the reduction of metal ions into nanosized particles by one-step preparation methods. MNPs have remarkable attractiveness in biomedical applications for their use as potential antioxidant, anticancer and antibacterial agents. The present review offers a comprehensive aspect of MNPs production via top-to-bottom and bottom-to-top approach with considerable emphasis on green technology and their possible biomedical applications. The critical parameters governing the MNPs formation by plant-based synthesis are also highlighted in this review.

Aim:The sustained release tablets of Aceclofenac were prepared and evaluated for the sustained release drug profile with an aim to reduce dosing frequency and provide patient compliance. Materials and Method: The tablets were prepared by using different percentages of Kollidon SR, Carbopol 934P and Eudragit L100 and their combination thereof by wet granulation method. The tablets were analyzed for post compression studies including thickness, diameter, mechanical strength and uniformity of content.The in vitro dissolution studies were carried out in pH 1.2 for first 2 h and in pH 6.8 buffer for total of 12 h. Results: The tablets exhibited acceptable physicochemical characteristics as per USP limits. The formulation containing Eudragit L100 failed to give the desired sustained release effect where as a slow drug release was observed in formulations containing Carbopol 934P. Therefore, a combination of pH dependant polymer (Eudragit L100) and pH independent polymer (Carbopol 934P) combination was used. The formulations were also prepared by Carbopol 934P with plastic polymer (Kollidon SR). The desired sustained release effect was given by latter combination at 2:1 concentration. Conclusion: This formulation, U13, followed zero order kinetics with non-Fickian drug release mechanism. When compared to the marketed brand by fit factor, U13 gave the ƒ2 value greater than 50 indicating closer proximity to the approved brand.