Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment

Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration. Inspired by natural lung surfactants, dipalmitoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DPPC/DMPG) surface-modified lipid nanoparticles (LNPs) were scrutinized for pulmonary administration. DPPC/DMPG-VRZ-LNPs prepared using ultrasonication/thin film hydration were investigated for colloidal properties over 3-month shelf storage. They were stable with a slight change in entrapment efficiency. They provided a sustained VRZ release over 24 h, with a rapid initial release. In vitro aerosolization indicated higher percentages of VRZ deposited on stages corresponding to secondary bronchi and alveolar ducts. Moreover, intrapulmonary administration maintained high lung VRZ concentration (27 ± 1.14 µg/g) after 6 h. A preclinical study using a cyclophosphamide-induced neutropenic rat model demonstrated a 3-fold reduction in BALF-Galactomannan down to 0.515 ± 0.22 µg/L confirming DPPC/DMPG-VRZ-LNPs potential in hyphal growth inhibition. Histopathological examination of infected/nontreated lung sections exhibited dense fungal load inside alveoli and blood vessels indicating massive tissue and angio-invasiveness. Nevertheless, DPPC/DMPG-VRZ-LNPs-treated animals displayed minimal hyphae with no signs of invasiveness. The developed bioinspired nanoparticles serve as prospective bioactive nanocarrier candidates for pulmonary administration of VRZ in the management of IPA

Maltodextrin: A Novel Excipient Used in Sugar-Based Orally Disintegrating Tablets and Phase Transition Process

The recent challenge in orally disintegrating tablets (ODT) manufacturing encompasses the compromise between instantaneous disintegration, sufficient hardness, and standard processing equipment. The current investigation constitutes one attempt to fulfill this challenge. Maltodextrin, in the present work, was utilized as a novel excipient to prepare ODT of meclizine. Tablets were prepared by both direct compression and wet granulation techniques. The effect of maltodextrin concentrations on ODT characteristics—manifested as hardness and disintegration time—was studied. The effect of conditioning (40°C and 75% relative humidity) as a post-compression treatment on ODT characteristics was also assessed. Furthermore, maltodextrin-pronounced hardening effect was investigated using differential scanning calorimetry (DSC) and X-ray analysis. Results revealed that in both techniques, rapid disintegration (30–40 s) would be achieved on the cost of tablet hardness (about 1 kg). Post-compression conditioning of tablets resulted in an increase in hardness (3 kg), while keeping rapid disintegration (30–40 s) according to guidance of the FDA for ODT. However, direct compression-conditioning technique exhibited drawbacks of long conditioning time and appearance of the so-called patch effect. These problems were, yet, absent in wet granulation-conditioning technique. DSC and X-ray analysis suggested involvement of glass-elastic deformation in maltodextrin hardening effect. High-performance liquid chromatography analysis of meclizine ODT suggested no degradation of the drug by the applied conditions of temperature and humidity. Overall results proposed that maltodextrin is a promising saccharide for production of ODT with accepted hardness-disintegration time compromise, utilizing standard processing equipment and phenomena of phase transition