Formulation development, characterization, and evaluation of bedaquiline fumarate - Soluplus® - solid dispersion.

Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.

Nanotechnology in Wastewater Management: A New Paradigm Towards Wastewater Treatment.

Clean and safe water is a fundamental human need for multi-faceted development of society and a thriving economy. Brisk rises in populations, expanding industrialization, urbanization and extensive agriculture practices have resulted in the generation of wastewater which have not only made the water dirty or polluted, but also deadly. Millions of people die every year due to diseases communicated through consumption of water contaminated by deleterious pathogens. Although various methods for wastewater treatment have been explored in the last few decades but their use is restrained by many limitations including use of chemicals, formation of disinfection by-products (DBPs), time consumption and expensiveness. Nanotechnology, manipulation of matter at a molecular or an atomic level to craft new structures, devices and systems having superior electronic, optical, magnetic, conductive and mechanical properties, is emerging as a promising technology, which has demonstrated remarkable feats in various fields including wastewater treatment. Nanomaterials encompass a high surface to volume ratio, a high sensitivity and reactivity, a high adsorption capacity, and ease of functionalization which makes them suitable for application in wastewater treatment. In this article we have reviewed the techniques being developed for wastewater treatment using nanotechnology based on adsorption and biosorption, nanofiltration, photocatalysis, disinfection and sensing technology. Furthermore, this review also highlights the fate of the nanomaterials in wastewater treatment as well as risks associated with their use.

Stable solid dispersion of lurasidone hydrochloride with augmented physicochemical properties for the treatment of schizophrenia and bipolar disorder.

Crystalline solid dispersion of lurasidone hydrochloride (LH) was made with various polar and non-polar small molecules to overcome the poor aqueous solubility issue. LH-Glutathione (GSH) solid dispersion in 1:1 ratio was prepared by co-grinding method and characterized by using differential scanning calorimetry (DSC), powder X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. GSH acts as antioxidant and reported for anti-schizophrenic activity may provide synergistic action with LH or reduce the side effects. LH in LH-GSH solid dispersion (SD) has shown improvement in solubility by 7.9 folds than plain drug which translated in terms of improved dissolution rate by two-folds. The in vitro dissolution results showed maximum dissolution rate with LH-GSH SD (97.85 ± 2.40%) compared to plain drug (50.5 ± 3.02%) at 15 min (t15 min, %) and thus, satisfying criteria of immediate release dosage form. DSC and FTIR data confirmed the stability of LH-GSH SD for 3 months at accelerated stability condition (40 ± 2°C and 75 ± 5% RH). The prepared LH-GSH SD can be used as a tool to target dual problems that is, enhanced physicochemical properties along with possible management of disorder which could be due to synergism with co-administered GSH. This approach is thought to be efficiently providing the relief to the psychological patients.

Bedaquiline fumarate microemulsion: formulation optimization, rheological characterization and in vitro studies.

Aim: Bedaquiline fumarate (BQF), an antitubercular drug, shows limited bioavailability due to solubility-limited intestinal absorption. In this research, the authors formulated a BQF-loaded microemulsion to improve BQF's oral bioavailability. Methods: Microemulsion was prepared by a spontaneous emulsification method and evaluated for thermodynamic stability, size, dispersibility, transmittance, rheology, microrheology, drug release, cytotoxicity and cellular uptake. Results: Microemulsion showed an average globule size of 26.50 ± 6.29 nm with spherical geometry and revealed gel-sol-gel behavior in microrheological studies. Cytotoxicity and cell uptake studies in Caco-2 cells showed that BQF microemulsion was cytocompatible at the highest concentration of 500 µg/ml with significantly higher cellular uptake than control. Conclusion: The present study indicates that BQF microemulsion could be explored further for effective treatment of multidrug-resistant tuberculosis.

Emerging trends and promises of nanoemulsions in therapeutics of infectious diseases.

Infectious diseases are prevalent and have contributed to high morbidity rates by creating havoc like the COVID-19, 1918 influenza and Black Death (the plague) pandemics. Antimicrobial resistance, adverse effects, the emergence of co-infections and the high cost of antimicrobial therapies are major threats to the health of people worldwide while impacting overall healthcare and socioeconomic development. One of the most common ways to address this issue lies in improving existing antimicrobial drug-delivery systems. Nanoemulsions and their modified forms have been successfully employed for the delivery of antimicrobials to treat infectious diseases. In this article, the authors comprehensively reviewed how nanoemulsion-based formulation systems are shifting the paradigm for therapeutics and diagnosis of infectious diseases.

Nanocrystals: An Overview of Fabrication, Characterization and Therapeutic Applications in Drug Delivery.

Approximately 40 % drugs in the market are having poor aqueous solubility related problems and 70 % molecules in discovery pipeline are being practically insoluble in water. Nanocrystals is a prominent tool to solve the issue related to poor aqueous solubility and helps in improving the bioavailability of many drugs as reported in the literature. Nanocrystals can be prepared by top down methods, bottom up methods and combination methods. Many patented products such as Nanocrystals®, DissoCubes®, NANOEDGE® and SmartCrystals ®, etc., are available, which are based on these three preparation methodologies. The particle size reduction resulted into unstable nanocrystalline system and the phenomenon of Ostawald ripening occurs. This instability issue could be resolved by using an appropriate stabilizers or combination of stabilizers. The nanosuspensions could be transformed to the solid state to prevent particle aggregation in liquid state by employing various unit operations such as lyophilisation, spray drying, granulation and pelletisation. These techniques are well known for their scalability and continuous nanocrystal formation advantages. Nanocrystals can be characterized by using scanning electron microscopy, transmission electron microscopy, atomic force microscopy, differential scanning calorimetry, fourier transform infrared spectroscopy, powdered x- ray diffraction and photon correlation spectroscopy. The downscaling of nanocrystals will enable rapid optimization of nanosuspension formulation in parallel screening design of preclinical developmental stage drug moieties. One of the most acceptable advantages of nanocrystals is their wide range of applicability such as oral delivery, ophthalmic delivery, pulmonary delivery, transdermal delivery, intravenous delivery and targeting (brain and tumor targeting). The enhancement in market value of nanocrystals as well as the amount of nanocrystal products in the market is gaining attention to be used as an approach in order to get commercial benefits.