Development of dissolving microneedles using a quality by design approach for transdermal delivery of the nanoemulsified volatile compound β-caryophyllene

• QbD-driven development of an integrated dissolvable MN system with nanoemulsion. • Understanding the impact of formulation variables on content maintenance and CQAs. • Proof of the viability of β-caryophyllene delivery through polymeric MN. • Promotion of transdermal release with association of nanoemulsion in polymeric MN. • Maintaining the content of the lipophilic and volatile compound in MN for 45 days. This study examines transdermal delivery of a β-caryophyllene (a lipophilic and volatile compound) loaded nanoemulsion from dissolving water-soluble polymer microneedles (microneedle array patches − MAPs). Development of this system was guided by the principles of Quality by Design; after defining a quality target product profile and critical quality attributes, a rational experimental plan optimized a formulation to maximize the β-caryophyllene content in MAPs. The optimized formulation consists of polyvinyl pyrrolidone combined with polyvinyl alcohol (combination ratio of 1.54) and a β-caryophyllene-to-polymer mass ratio of 0.09. The β-caryophyllene content was maintained higher than 95 % in relation to the additional mass following the micromolding process and after 45 days of storage. In vitro skin insertion, dissolution, mechanical properties, and transdermal delivery have been investigated for the prototype. A key feature of this work is demonstrating the feasibility of delivering a volatile compound through MAP by associating it with a nanoemulsion. This combined delivery method allows for the transdermal administration of β-caryophyllene, which cannot be achieved through topical nanoemulsion application alone. Overall, the developed system offers a promising alternative to traditional topical and oral pharmaceutical dosage forms.