Novel in situ forming hydrogel microneedles were evaluated for transdermal drug delivery using a biocompatible non-ionic triblock amphiphilic thermosensitive copolymer. The transition property of poloxamer from solution at room temperature to gel at skin temperature (32 °C) was utilized in preparation of in situ forming hydrogel microneedles. Methotrexate has been used to treat solid tumors, but because of its narrow safety margin, it requires sustained delivery within the therapeutic window. Formulations with and without poloxamer at different methotrexate concentrations were prepared and evaluated for drug permeation across skin using vertical Franz diffusion cell for 72 h. Sol-gel transition, skin resistance and thickness, microneedles geometry, microchannel depth, shape, formation and uniformity, viscoelasticity of skin, and in vitro drug permeation were characterized and tested. An average cumulative drug amount of 32.2 ± 15.76 and 114.54 ± 40.89 μg/cm for porcine ear skin and 3.89 ± 0.60 and 10.27 ± 6.98 μg/cm for dermatomed human skin from 0.2 % w/w and 0.4 % w/w methotrexate formulations was delivered by the in situ forming hydrogel microneedles. These in situ hydrogel microneedles embedded within the porated site of the skin provided a steady and sustained drug delivery.
The quality of a pharmaceutical dosage form is the foremost criterion during the development of a product. The quality by testing (QbT) technique used by the pharmaceutical industry to ensure the quality of a drug product is a rigid process with tight specifications. The specifications set by QbT are not essentially based upon the critical quality attributes of the materials and critical process parameters involved in development, but based upon recorded observation of manufactured batches. Room for flexibility is narrow as every level change requires submission of a supplement to the US Food Drug and Administration. Unlike QbT, the concept of quality by design (QbD) is a modern approach to ensure the quality of pharmaceutical products. It can identify the critical attributes of the material and the process parameters involved in development of the drug product through substantial scientific understanding with an established design space. QbD tools such as design of experiment, risk assessment, and process analytical technology help to establish a control strategy for every drug product with an option of continual monitoring and improvement for a quality drug product. Implementing the concept of QbD to topical dermatological dosage forms is in the initial stages. For a generic topical dermatological dosage form, establishing the required pharmaceutical and therapeutic equivalence with same components or qualitatively (Q1), same components with same concentration or quantitatively (Q2), and same components in same concentration with same arrangement (Q3) is a cumbersome process. Applying QbD approaches by defining a quality target product profile and identifying critical quality attributes with establishment of a design space and control strategy can guide the design of a quality-based generic topical dermatological product.
Constant efforts for HIV prevention using antiretroviral drugs, pre- and postexposure prophylactic agents, and microbicides are being made by researchers. Drug-delivery systems such as oral tablets and coitally dependent vaginal gels are short acting, require daily application, and are associated with user adherence issues, whereas the coitally independent systems such as injectables and biodegradable implants are long acting, lasting several months, during which time the termination of prophylaxis is impractical in case of adverse effects. An effective drug-delivery system to be used for an intermediate duration, if available, would be an attractive alternative option for users in terms of adherence. Transdermal delivery systems, overcoming most of the limitations of the other routes of administration and aiming to provide sustained delivery of drugs through skin, may be explored for HIV prevention. Passive and physical enhancement techniques may be designed strategically to improve the transdermal delivery of HIV preventive agents.
Poloxamer formulation with 0.1% w/w piroxicam delivered a cumulative amount of 11.99 ± 7.82 and 11.23 ± 1.79 μg/cm(2), while non-poloxamer formulation delivered 3.57 ± 2.20 and 4.60 ± 6.90 μg/cm(2) with 0.1 and 0.5 ml artificial saliva, respectively, through porcine sublingual tissue in 6 h. A similar delivery profile was observed for 0.05% w/w piroxicam formulation as well.
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