Nanoparticle Engineering of Aprepitant Using Nano-by-Design (NbD) Approach.

The aim of this research was to develop a nanosuspension of aprepitant (APT) using the Nano-by-Design approach. A novel microfluidization technology was used for processing the formulation. A 32 full factorial design was used for the optimization of dependent variables, which included critical quality attributes like particle size and polydispersity index. Subsequently, the design space was generated and the optimum formulation was located using desirability constraints followed by its validation.The prepared nanosuspension had a particle size of 721 nm ± 5%, a polydispersity index of 0.106 ± 3%, and a zeta potential of - 8.06 ± 5 mV. Its surface morphology was studied using SEM, DSC, and XRD. It revealed that the prepared nanosuspension had a nano-crystalline nature. The process parameters did not lead to any physicochemical interaction between the drug and excipients. This was confirmed using FTIR analysis. In vitro dissolution studies revealed 100% cumulative drug release over 60 min, showing better results in comparison with pure APT. Thus, it has been shown that microfluidization can be an industrially feasible, novel, green technology for the preparation of a stable APT nanosuspension for improving the dissolution profile of the drug.

Formulation development of nanostructured lipid carrier-based nanogels encapsulating tacrolimus for sustained therapy of psoriasis.

The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated. Ex vivo cytotoxicity of the formulation was assessed in murine fibroblast cells. Oxazolone and imiquimod models of psoriasis were used to assess the effectiveness of the nanogel. The NLCs exhibited a submicron particle size of 320 ± 10 nm, a low polydispersity index (<0.3), and a zeta potential of -19.4 mV. Morphological analysis revealed spherical nanoparticles with an encapsulation efficiency of 60 ± 3 %. The nanogel maintained a pH of 6.0 ± 0.5 and possessed a remarkable drug content of 99.73 ± 1.4 %. It exhibited pseudoplastic flow behaviour, ensuring easy spreadability, and demonstrated sustained drug release exceeding 90 % over a 24-hr period. Ex vivo cytotoxicity assessments revealed that the nanogel was safe because no cell death was induced. Nanogel resolved psoriatic blisters, was non-irritating and improved skin elasticity. The favorable properties, safety profile, and remarkable efficacy show the potential of the nanogel as a patient-friendly and effective therapeutic option for psoriasis treatment.

Gellan gum-based in situ gelling ophthalmic nanosuspension of Posaconazole.

The formulation and delivery of highly hydrophobic drugs in an optimized dosage form is challenging to formulation scientists. Posaconazole has shown promising action in case studies against fungal keratitis. Biological macromolecules like gellan gum would aid in enhancing the availability of such drugs by increasing the contact time of the formulation. Herein, we propose a transmucosal ocular delivery system of Posaconazole by developing a gellan gum-based in situ gelling nanosuspension. The HPLC method for Posaconazole was developed and validated as per ICH guidelines. The nanosuspension was prepared by microfluidization and optimized by Quality by Design. The gellan gum concentration selected was 0.4% w/v based on the viscosity and mucoadhesion measurements. A greater zone of inhibition of ~ 15 mm was observed for the prepared nanosuspension as compared to ~ 11 mm for the marketed itraconazole nanosuspension. A potential irritancy score of 0.85, considered to be non-irritant, was observed for the developed nanosuspension. Higher drug release of ~ 35% was noted for the nanosuspension compared to about ~ 10% for the coarse suspension. Ex vivo corneal retention studies on excised goat cornea demonstrated ~ 70% drug retention in the tissue. Graphical abstract depicting the central hypothesis of the work.

Carbohydrate anchored lipid nanoparticles.

Nanotechnology has been a dynamic field for formulation scientists with multidisciplinary research being conducted worldwide. Advancements in development of functional nanosystems have led to evolution of breakthrough technologies. Lipidic nanosystems, in particular, are highly preferred owing to their non-immunogenic safety profiles along with a range of versatile intrinsic properties. Surface modification of lipid nanoparticles by anchoring carbohydrates to these systems is one such attractive drug delivery technology. Carbohydrates confer interesting properties to the nanosystems such as stealth, biostability, bioavailability, reduced toxicity due to decreased immunogenic response, targeting potential as well as ease of commercial availability. The carbohydrate anchored systems can be developed using methods such as adsorption, incorporation (nanoprecipitation or solvent displacement method), crosslinking and grafting. Current review provides a detailed overview of potential lipid based nanoparticulate systems with an emphasis on liposomes, solid lipid nanoparticles, nanostructures lipid carriers and micelles. Review further explores basics of surface modification, methods applied therein, advantages of carbohydrates as surface modifiers, their versatile applications, techniques for characterization of carbohydrate anchored systems and vital regulatory aspects concerned with these specialized systems.

Surface Engineering of Fenofibrate Nanocrystals Using Nano-by-Design Multivariate Integration: A Biopharmaceutical and Pharmacokinetic Perspective.

INTRODUCTION: Surface engineering of nanocrystals for improving the biopharmaceutical features is a multivariate process involving numerous formulation and process variables, thus making it a complicated process to get the desired biopharmaceutical quality profile. Nano-by-design is hereby proposed as an approach to nanonize an orally active, lipid-lowering fenofibrate in order to improve feasibility of product development. METHODOLOGY: Top-down wet ball milling (media milling) in zirconia planetary chamber was methodically explored for improving the solubility and bioavailability of fenofibrate by formulating a nanosuspension using polyvinyl alcohol as a stabilizer. Several influencing variables were screened using a systematic one-factor-at-a-time approach. DSC, SEM, XRD, and FTIR were utilized for physical characterization of the product during the development stage and to study the effect of milling time, milling speed, fenofibrate:stabilizer ratio, premilling time and stabilizer concentration. Potential risk factors affecting critical quality biopharmaceutical attributes of fenofibrate nanocrystals like size, zeta potential, in vitro release, crystallinity and intrinsic solubility were optimized to improve pharmacokinetic performance. RESULT: Formulated nanosized fenofibrate exhibited a crystalize nature as evident from XRD and DSC, 411 nm size, and a rapid but complete dissolution (~99% in 30 min). This resulted in a quick onset of action and improved bioavailability as observed from 51.46% shorter Tmax, 82.63% higher Cmax, and 69.34% higher AUC0-24h, respectively.

Development of Atovaquone Nanosuspension: Quality by Design Approach.

OBJECTIVE: The present study reports the use of MicrofluidizerTM technology to form a stable nanosuspension of atovaquone (ATQ) using quality by design (QbD) approach. METHODS: The patient-centric quality target product profile and critical quality attributes (CQAs) were identified. A Box-Behnken design was employed for the optimization of dependent variables, while CQAs like particle size and PDI were evaluated as response variables. Effective optimization of ATQ nanosuspension preparation using Microfluidizer processor as a novel green technology was achieved using QbD approach. RESULT: The prepared nanosuspension had a mean particle size of 865 nm ± 5%, PDI of 0.261 ± 3%, and zeta potential of -1.79 ± 5 mV. The characterization of the prepared nanosuspension by SEM, DSC, and XRD revealed its nano-crystalline nature whereas FTIR spectroscopic analysis confirmed the absence of any physicochemical interaction because of process parameters between the drug and excipients. CONCLUSION: In vitro dissolution studies of the nanosuspension using USP-IV exhibited a 100% cumulative drug release over 90 minutes, which is significantly better than that of ATQ pure API. In vivo pharmacokinetic studies revealed bioequivalence of ATQ nanosuspensions by Microfluidizer homogenization process to the marketed formulation1.

Multidimensional Ophthalmic Nanosystems for Molecular Detection and Therapy of Eye Disorders.

Symptomatic distresses associated with common ophthalmic infections and their persistence, have remained a tribulation with repeated occurrences. Although being a directly accessible organ, traditional therapeutic strategies exhibiting seemingly fruitful outcome in treatment and prognosis of eye disorders call for improvement in disease intervention. This is due to frequent challenges presented by the ophthalmic environment. Contemporary research has addressed these challenges by applying nanotechnology as a central concept in designing more proficient diagnostic and therapeutic systems for eye ailments. Within such nanosystems (dendrimers, aptamers, metal nanoparticles, etc.), bioactive agents, drugs and genetic materials can be entrapped and these form the key elements that act at the biomolecular stage and bestow a high level of efficacy towards eradication of disease causatives and specificity for recognition and capture aiding diagnostic processes. In the current review, we present researched and patented nanocentric technologies as promising tools in detection and treatment of ophthalmic ailments.