(T0930-11-72) Enhanced Transdermal Delivery of Lurasidone for Potential Treatment of Schizophrenia

Purpose: Lurasidone is an atypical antipsychotic medication that has been shown to be effective in reducing the symptoms of schizophrenia and major depressive disorder, making it a valuable treatment option for individuals with these conditions. It works by blocking dopamine and serotonin receptors in the brain, which helps to control psychotic symptoms and stabilize mood. It is available only as oral tablets with bioavailability of 9-19%. However, its oral administration is associated with several adverse effects, including gastrointestinal disturbances, weight gain, and metabolic abnormalities. Transdermal delivery of lurasidone offers several advantages over oral administration, including reduced side effects, enhanced therapeutic efficacy, avoidance of first-pass metabolism, and reduced dosing frequency, thus improving the patient adherence which is an obstacle in treating schizophrenia. In this study, we investigate the passive delivery, delivery with the help of chemical enhancer, and delivery of lurasidone in the intact and microneedle-treated skin with Dr. PenTM Ultima A6.

Methods: In vitro permeation test (IVPT) was performed on dermatomed porcine ear skin using vertical Franz diffusion cells. samples (0.3 ml) were withdrawn from the receptor at a set time point for 72 h and subjected to a validated HPLC method for analyzing the delivery to the receptor. IVPT studies were performed using 90% of saturation solubility of lurasidone in each vehicle as donor. The passive delivery was determined using propylene glycol as the vehicle. The three chemical enhancers that have been used are oleic acid (25% w/w), transcutol (5 % w/w), and oleyl alcohol (10% w/w), all in propylene glycol. In microneedle treated group, acetic acid with pH 3 was used as a vehicle.

Results: The saturation solubility of lurasidone in propylene glycol, oleic acid (25% w/w), transcutol (5 % w/w), and oleyl alcohol (10% w/w) were found to be 0.86 mg/ml, 1.6 mg/ml, 5 mg/ml, and 3.1 mg/ml respectively. The drug content for microneedle treated group was 0.25 mg/cm2. IVPT studies found that transcutol (65.60 ± 11.88 µg/cm2) increased the penetration of lurasidone more in compared to other chemical enhancers and there was no passive permeation detected. In the microneedle-treated study the use of Dr. PenTM Ultima A6 had increased the delivery significantly (46.74 ± 2.9 µg/cm2). However, the drug did not permeate across the skin significantly to reach the target for three days (191 µg/cm2) which could be due to higher than ideal lipophilicity nature of lurasidone (logP:4.5).

Conclusion: The feasibility of transdermal delivery of the highly lipophilic drug, lurasidone was established. Chemical enhancers were able to significantly increase lurasidone permeation across the skin. The amount of drug that permeated the receptor in microneedle treated groups indicates a potential in achieving target drug delivery upon further exploration of enhancement strategies.

Figure 1: comparison of the average amount of lurasidone delivered to the receptor (a) passive permeation versus the use of chemical enhancers oleic acid (25% w/w), transcutol (5 % w/w), and oleyl alcohol (10% w/w).

(b) passive permeation versus microneedle-treated skin with Dr. PenTM Ultima A6.