Abstract
The poor aqueous solubility of existing and emerging drugs is a major issue faced by the pharmaceutical industry. Water-miscible organic solvents, termed co-solvents, can be used to enhance the solubility of poorly soluble substances. Typically, drugs with poor aqueous solubility and Log P > 3 are not amenable to delivery across the skin. This study investigated the use of co-solvents as reservoirs to be used in combination with hydrogel-forming microneedles to enhance the transdermal delivery of hydrophobic compounds, namely Nile red, olanzapine and atorvastatin. A custom-made Franz cell apparatus was fabricated to test the suitability of a liquid drug reservoir in combination with polymeric microneedles. A co-solvency approach to reservoir formulation proved effective, with 83.30% ± 9.38% of Nile red dye, dissolved in 1 mL poly(ethylene glycol) (PEG 400), permeating neonatal porcine skin over 24 h. PEG 400 and propylene glycol were found to be suitable reservoir media for olanzapine and atorvastatin, with approximately 50% of each drug delivered after 24 h. This work provides crucial proof-of-concept evidence that the manipulation of microneedle reservoir properties is an effective method to facilitate microneedle-mediated delivery of hydrophobic compounds.
Highlights
Poor drug solubility is a major challenge of many new and emerging therapeutic agents
Poly(ethylene glycol) (PEG; MW 10,000, 600, 400 and 200 Da), methylene blue and HPLC grade methanol and acetonitrile were purchased from Sigma–Aldrich (Dorset, UK)
There was virtually no swelling of the baseplate when immersed in PEG 400 for 24 h (
Summary
Poor drug solubility is a major challenge of many new and emerging therapeutic agents. It is frequently cited that 40% of recently marketed drug compounds have limited solubility in aqueous media [1], with this figure higher again for drugs in the developmental stage (>70%) [2] This is problematic for several reasons, with one of the major issues being unacceptably poor drug bioavailability. To capitalise on the therapeutic potential of drugs that are promising in developmental stages but hampered by formulation issues due to their solubility profile, a variety of solubility enhancement strategies can be used [4]. These techniques are most commonly used for medications delivered orally but are not limited to this route of administration
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