The College of Pharmacy discussed the PhD dissertation entitled “Formulation, In-vitro and In-vivo Evaluation of Olanzapine Nanoparticles Dissolving Microneedles for Transdermal Delivery” by the student Abulfadhel Jaber Neamah and the supervisor, Professor. Dr. Mowafaq M. Ghareeb, at the Pharmaceutics Department. The study aimed to formulate and evaluate OLZ nanoparticles dissolving microneedles for transdermal delivery to obtain a rapid onset of drug action and ease of administration of the medicine for schizophrenic patients, in addition to enhancing the bioavailability of the drug. The nanoprecipitation technique was applied for the preparation of OLZ nanosuspension by using different polymers with various ratios. Nanosuspension was evaluated using different methods, including particle size, polydispersity index (PDI), entrapment efficiency (EE%), zeta potential and an in vitro release study. The morphology was evaluated by a field emission scanning electron microscope (FESEM) and an atomic force microscope (AFM). Dissolving microneedles (MNs) patches were prepared by loading the optimized formula of OLZ nanosuspension into polydimethylsiloxane (PDMS) micromolds cavities, followed by casting the polymeric solution of polyvinylpyrrolidone (PVP-K30), and polyvinyl alcohol (PVA) to form MNs matrix, the prepared MNs patches were evaluated for morphology, mechanical strength, drug content, ex vivo permeation study, and in vivo pharmacokinetic parameters. The results of characterization studies revealed that the optimized formula of OLZ nanosuspension was OLZ-14, which was composed of OLZ and Soluplus®) in a ratio 1:2. The average size of particles, PDI, EE%, and zeta potential of OLZ-14 were manifested to be 115.7±5.45 nm, 0.240±0.070, 79.4±5.46%, and -19.01 mV, respectively. OLZ-14 exhibited a higher and significant drug release (p < 0.05) as compared with other formulations and pure drugs. FESEM and AFM show spherical shapes of nanoparticles with sizes similar to that obtained by the zeta sizer. So, OLZ-14 was utilized for the fabrication of MNs. The results of MNs preparation indicate that MN-5 exhibits a sharp needle with good mechanical strength according to texture analysis, a high drug content of 98.52%, ex vivo permeation study that exhibited that MN-5 permeates more effectively through rabbit skin as compared to a simple patch by approximately 5.54-fold. A pharmacokinetics study revealed that the MN-5 patch exhibited a higher Cmax of 138.7±8.56 ng/ml and a lower Tmax of 2.5 hr as compared to the marketed tablet of OLZ, which had a Cmax of 119.6±4.51 ng/ml and a Tmax 6 hr. AUC0-∞ of MN-5 was 6054.56±376 ng. h/ml, which was higher than AUC0-∞ of the marketed tablet 3975.77±373 ng. h/ml. In conclusion, the dissolving MN-5 patch can be considered a promising formula to obtain a rapid onset of OLZ action, facilitate the administration of medicine for schizophrenic patients as compared with oral conventional tablets, and enhance the bioavailability of the drug. The study recommended conducting a large study for the research project by increasing the number of laboratory animals to compare with other ordinary patches and to verify the obtained results. And submitting the research project to one of the pharmaceutical companies to study it for the purpose of performing a bioequivalence study on healthy volunteers to determine the therapeutic effectiveness of the pharmaceutical dosage form in order to be able to manufacture and market it. In addition to conducting studies and reviews to evaluate patients’ compliance and acceptability of dissolvable microneedle patches over conventional oral dosage forms.
