Development of lysozyme loaded microneedles for dermal applications.

Microneedles are being widely explored for dermal delivery of macromolecules. They have the capability and the potential for entrapping enzymes such as lysozyme within a polymeric matrix that do not alter the protein integrity, enable a bolus or a sustained release. In this study, polymeric microneedles have been used to entrap lysozyme (14 kDa) using biodegradable and dissolving polymers such as Polyvinylpyrrolidone (PVP), Hyaluronic acid (HA), and Poly lactic co glycolic acid (PLGA). Microneedles were fabricated using mold casting technique. The structural strength was determined using texture analyzer where PLGA microneedles (16.56 ± 0.23 g) required a significantly higher puncture force as compared to PVP and HA microneedles (12.10 ± 0.04 g and 11.40 ± 0.32 g respectively). The release profile showed an instantaneous release in the case of PVP and HA with almost 50% of the drug released within the first 20 min in both cases and remaining drug was released within the next 2 h whereas Lysozyme entrapped in PLGA showed a release of 29.53 ± 0.78% of lysozyme 72 h. Lysozyme entrapped in microneedles was characterized using circular dichroism and SDS-page analysis for structural stability post microneedle fabrication. The stability studies were performed on these polymeric microneedles for understanding its delivery potential of bio-active lysozyme. At the end of 90 days lysozyme concentration entrapped was 90.35 ± 0.06% 93.76 ± 0.34% 91.74 ± 0.37% for PVP, HA and PLGA respectively. The protein integrity remained intact for three months (α + ß) sheets remained intact in the three different polymeric microneedles. The enzyme assay showed that the enzyme entrapped inside microneedles is biologically active and could be used to lyse bacterial infections for dermal applications. However, a detailed analysis of protein formulations would be useful for extending microneedles applications in wounds, skin infections.

Effect of Mild Hyperthermia on Transdermal Absorption of Nicotine from Patches.

Application of heat (hyperthermic conditions) on skin is known to enhance drug transfer and facilitate skin penetration of molecules. The aim of this work was to study the effect of hyperthermia on the drug release and skin permeation from nicotine transdermal patches. The drug release and skin permeation were characterized by in vitro release test and in vitro permeation test. The temperature was maintained at 32 °C as control (simulating normal physiological skin temperature) and 42 °C as hyperthermia condition. The in vitro release test was carried out using USP apparatus 5-Paddle over disk method for a transdermal patch. Skin permeation study was carried out across porcine skin using the flow through cells (PermeGear, Inc.) with an active diffusion area of 0.94 cm2. Mechanistic studies (parameters such as partition coefficient, TEWL and electrical resistivity) were also performed to understand the mechanisms involved in determining the influence of hyperthermia on drug delivery from transdermal patches of nicotine. The rate and extent of drug release from nicotine patch was not significantly different at two temperatures (Cumulative release after 12 h was 43.99 ± 3.29% at 32 °C and 53.70 ± 5.14% at 42 °C). Whereas, in case of in vitro permeation studies, the nicotine transdermal permeation flux for patch was threefold higher at 42 °C (100.1 ± 14.83 µg/cm2/h) than at 32 °C (33.3 ± 14.83 µg/cm2/h). The mechanistic studies revealed that the predominant mechanism of enhancement of drug permeation by hyperthermia condition is by the way of increasing the skin permeability. There is a potential concern of dumping of higher dose of nicotine via transdermal route.

Solid-State Stability Issues of Drugs in Transdermal Patch Formulations.

The transdermal patch formulation has many advantages, including noninvasiveness, an ability to bypass the first-pass metabolism, low dosage requirements, and prolonged drug delivery. However, the instability of solid-state drugs is one of the most critical problems observed in transdermal patch products. Therefore, a well-characterized approach for counteracting stability problems in solid-state drugs is crucial for improving the performance of transdermal patch products. This review provides insight into the solid-state stability of drugs associated with transdermal patch products and offers a comprehensive update on the various approaches being used for improving the stability of the active pharmaceutical ingredients currently being used.