Drug Delivery Letters - Volume 13, Issue 1, 2023

Phytopharmaceuticals are herbal medicines that include standardized extracts, bioactive fractions, and purified phytoconstituents. They have been used for the cure, treatment, and mitigation of diseases since ancient times. Phytopharmaceuticals have a wide array of health benefits but their therapeutic efficacy is limited due to poor absorption, low bioavailability, and early elimination profile. A novel phospholipid complex is a newly introduced patented technology initially developed to incorporate standardized plant extracts/fractions or water-soluble phytoconstituents into phospholipids to produce a lipid compatible molecular complex, called phytosome, which improves their absorption and bioavailability. In herbal formulations, phytosome is the most advanced dosage form that has upgraded absorption rate and improved pharmacokinetics in comparison with conventional products. Phospholipid-complex is the result of hydrogen bonding between phospholipids and phytoconstituents, which offers maximum incorporation of herbal active ingredients into the lipidic layer and core. The increased therapeutic efficacy is due to the formation of amphiphilic phospholipid complex of herbal medicine. This review highlights the role of phospholipids in the delivery of herbal bioactives and natural extracts with special emphasis on phytosomes. Moreover, the current status of bioavailabilities, commercial products, patents, and clinical trials of phytosomal system of phytopharmaceuticals were addressed.

Rheumatoid arthritis (RA) is a well-known chronic inflammatory disease that results in articular degradation, comorbidities, and body part functional loss. In the last two decades, the development of effective biologics and small compounds, such as Janus kinase inhibitors (Jakinibs), has significantly improved clinical outcomes. Low-molecular-weight chemicals known as jakinibs are currently used for effective treatment of RA. Jakinibs are a new class of drugs being developed to treat RA, and several of them are now in different phases of clinical trials to establish their safety and efficacy in humans. Jakinibs can be very different in their selectivity against JAK inhibitors. For an efficient therapy of RA, it is critical to fully comprehend the properties of JAK inhibitors as well as their mechanism of action. Tofacitinib, Baricitinib, Upadacitinib, Peficitinib, Filgotinib, Decernotinib, Itacitinib, Ruxolitinib, and PF-06651600 are a few selective orally active Jakinibs that have entered clinical trials to treat RA. This review aims to elaborate on Jakinibs for the treatment of Rheumatoid Arthritis (RH), including their mechanism of action (MOA), efficacy and safety profiles, clinical trials of adverse effects (AEs) associated with Jakinibs and combination therapy with other DMARDs.

Background: The current study explores the enhancement of solubility and dissolution rate of a poorly water-soluble drug Iloperidone (IPD) by synthesizing co-crystals (CC) using 4- amino benzoic acid (ABA) as a coformer. Methods: Pharmaceutical CCs of IPD with ABA were designed and synthesized using crystal engineering. CCs were prepared by solvent evaporation (SE) technique and studied for their enhancement in solubility and dissolution rate. CC formation was confirmed by Fourier Transform Infra- Red Spectroscopy (FTIR), powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Proton Nuclear Magnetic Resonance (¹H- NMR). Results: Structural characterization studies exhibited new characteristic peaks, which confirmed that CCs could be generated from IPD and ABA using SE technique. The apparent aqueous solubility studies of the CCs exhibited 7.1 folds increase in solubility compared to the pure drug. Improvement in the rate of dissolution of CCs was evident from the in vitro dissolution studies, where CCs displayed 94.15 ± 0.27% drug release in 60min while pure drug showed only 39.90 ± 1.86% release in the same time period. Conclusion: CCs of IPD and ABA provide a novel approach to overcoming the solubility issues.

Background: Topical therapy for nail infection has a serious drawback of drug permeation via keratinized human nail plate. Onychomycosis, or tinea unguium, is a human nail fungal infection affecting nearly 19% of the world’s population. Aim: Purposely, we aimed to develop and evaluate nail lacquer formulations incorporated with luliconazole utilizing different permeation enhancers for targeted transungual drug delivery. Nail clippings were treated with luliconazole solution (5% w/v) with or without permeation enhancers and screened by determining the hydration enhancement factor and retention of the drug in the nail clippings. Different batches of nail lacquer formulations were prepared to employ Eudragit, polyethylene glycol 400, Tween 80, and permeation enhancer with the highest hydration enhancement factor value. Methods: Successively, the formulations were evaluated for studies like compatibility, application, gloss, blush, smoothness of flow, adhesion, non-volatile content, etc. Based on the results of physical characterization and in vitro release study, formulations based on Eudragit RLPO and RSPO containing N-acetylcysteine and urea and the Eudragit RL100 containing urea as penetration enhancer were found to be potentially useful. Furthermore, a comparative ex vivo evaluation of the formulations for permeation across the nail clippings revealed that the luliconazole-loaded Eudragit RLPO formulations containing N-acetylcysteine and urea provided the highest flux (5.12 μg/cm²/min) and shortest lag time (17.4 min). Results: Morphological analysis showed an increase in the number of pores on the nail surface, leading to the enhancement of drug diffusion across the nail matrix and nail bed. Conclusion: Furthermore, the luliconazole nail lacquer formulation exhibited higher antifungal activity, viscosity, and stability properties. Hence, the results suggest that the developed luliconazole nail lacquer formulation is an efficient topical transungual drug delivery system.

Background: Owing to presystemic metabolism following oral drug delivery, most antihypertensive medications have a low bioavailability. Cilnidipine is a calcium channel blocker used to treat mild to moderate hypertension. Cilnidipine's bioavailability is reduced by 13% due to substantial presystemic metabolism. Objective: The study aimed to fabricate non-irritant and stable microsponge-based hydrogel to enhance the bioavailability of cilnidipine, a weakly water-soluble medication. In addition, the goal was to enhance the permeation rate and retention time at the site of application. Methods: Formulation was developed by using a two-level factorial design with Design Expert software version 13 (14-day free trial). Microsponges were formulated by the emulsion solvent diffusion method, followed by evaluating responses, such as particle size, percentage entrapment efficiency, in vitro drug release, and surface morphology. In addition, X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FT-IR) were performed. Viscosity, swelling behaviour, spreadability, in vitro diffusion, skin irritancy using Wistar albino rats, and in vitro permeation using goat skin were assessed, and stability studies were performed after incorporating the finest formulation into the gel base. Results: Fabricated microsponges were found to be within the required micro dimensions having the necessary porous morphology as demonstrated by scanning electron microscopy studies. Drug entrapment efficiency was found to be in the range of 75-88%. The extended medicament release duration of up to 8 hours was observed. The diffusion data showed controlled release, as demonstrated by Higuchi’s plot. In vitro permeation studies displayed enhanced medicament retention and permeation rate at the site of application. Conclusion: The fabricated microsponge drug delivery system was found to be stable, non-irritant, and having enhanced permeation rate and retention time.

Background: In humans, Carotenoids are important in scavenging singlet oxygen and peroxyl radicals. Lutein has been demonstrated in multiple studies to help protect the skin from photodamage, as well as provide a variety of other health advantages. In the recent decade, the topical use of Lutein as a new ultraviolet (UV) protectant, anti-stress, and blue light filter capable of protecting skin from photodamage has piqued cosmetic and pharmacological attention. Because Lutein is insoluble, it was integrated into nanocarriers for topical administration. Objective: The objective of this study was to formulate an NLC-based sunscreen gel of Lutein. Methods: Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration technique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading (DL), encapsulation efficacy (EE), and in vitro drug release. The optimised formula was incorporated into a gel base and an in-vitro sun protection factor (SPF) was determined. Ex- vivo permeation study was performed on rat skin using a Franz diffusion cell. Cocoa butter and rose oil were chosen as solid and liquid lipids for NLC formulation. Results: The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC5) were found to be 81.64 nm, 0.463, -14.1mV, 79.90 %, and 89.86% respectively. The SPF value of the Lutein-NLC-loaded gel was found to be 27.524. The drug flux Jss from NLC gel was measured in the range of 0.07955 g/cm²/h. Conclusion: The investigation suggested lipid nanoparticles as a suitable carrier for Lutein to be delivered as sunscreen gel.