Articulating the Pharmacological and Nanotechnological Aspects of Genistein: Current and Future Prospectives.

Throughout the past several centuries, herbal constituents have been the subject of scientific interest and the latest research into their therapeutic potential is underway. Genistein is a soy-derived isoflavone found in huge amounts in soy, along with the plants of the Fabaceae family. Scientific studies have demonstrated the beneficial effects of genistein on various health conditions. Genistein presents a broad range of pharmacological activities, including anticancer, neuroprotective, cardioprotective, antiulcer, anti-diabetic, wound healing, anti-bacterial, antiviral, skin, and radioprotective effects. However, the hydrophobic nature of genistein results in constrained absorption and restricts its therapeutic potential. In this review, the number of nanocarriers for genistein delivery has been explored, such as polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles, liposomes, micelles, transferosomes, and nanoemulsions and nanofibers. These nano-formulations of genistein have been utilized as a potential strategy for various disorders, employing a variety of ex vivo, in vitro, and in vivo models and various administration routes. This review concluded that genistein is a potential therapeutic agent for treating various diseases, including cancer, neurodegenerative disorders, cardiovascular disorders, obesity, diabetes, ulcers, etc., when formulated in suitable nanocarriers.

Novel Arena of Nanocosmetics: Applications and their Remarkable Contribution in the Management of Dermal Disorders, Topical Delivery, Future Trends and Challenges.

Nanocosmetics have attracted a considerable audience towards natural care due to their low cost, target-specific delivery, and reduced toxicity compared to chemical-based cosmetics. Nanofomulations, including nanoemulsions, nanotubes, and polymeric carriers, have become next-generation products explored for the multifaced applications of nanotechnology in skin care. The rise in the cosmetic industry demands innovative and personalized products designed using nanocarriers for better targeting and improving patient compliance. Furthermore, nanocosmetics increase the efficiency of skin permeation active ingredient entrapment, providing better UV protection. Moreover, it offers controlled drug release, targeting active sites and enhancing physical stability. Further, overcoming the drawback of penetration problems makes them sustainable formulations for precision medicine. Skincare nourishment with nanocosmetics using Indian spices helps to maintain, beautify, and rejuvenate human skin. Nanophytopharmaceuticals extracted from plants, including alkaloids, flavonoids, antioxidants, and volatile oils, are essential phyto-products for skin care. Nano herbals and nanocosmetics are a growing market and gift of nature that nourishes and cures skin ailments like acne, pemphigus, anti-aging, albinism, psoriasis, and fungal infections. The emerging concern is highlighted in the investigation of nanoformulation toxicity and safety concerns in skin care. Further, it helps to manifest research, development, and innovation in expanding the scope of herbal industries.

Imaging and Non-imaging Analytical Techniques Used for Drug Nanosizing and their Patents: An Overview.

BACKGROUND: Nanosizing is widely recognized as an effective technique for improving the solubility, dissolution rate, onset of action, and bioavailability of poorly water-soluble drugs. To control the execution and behavior of the output product, more advanced and valuable analytical techniques are required. OBJECTIVE: The primary intent of this review manuscript was to furnish the understanding of imaging and non-imaging techniques related to nanosizing analysis by focusing on related patents. In addition, the study also aimed to collect and illustrate the information on various classical (laser diffractometry, photon correlation spectroscopy, zeta potential, laser Doppler electrophoresis, X-ray diffractometry, differential scanning calorimeter, scanning electron microscopy, transmission electron microscopy), new, and advanced analytical techniques (improved dynamic light scattering method, Brunauer-EmmettTeller method, ultrasonic attenuation, biosensor), as well as commercial techniques, like inductively coupled plasma mass spectroscopy, aerodynamic particle sizer, scanning mobility particle sizer, and matrix-assisted laser desorption/ionization mass spectroscopy, which all relate to nano-sized particles. METHODS: The present manuscript has taken a fresh look at the various aspects of the analytical techniques utilized in the process of nanosizing, and has achieved this through the analysis of a wide range of peer-reviewed literature. All summarized literature studies provide the information that can meet the basic needs of nanotechnology. RESULTS: A variety of analytical techniques related to the nanosizing process have already been established and have great potential to weed out several issues. However, the current scenarios require more relevant, accurate, and advanced analytical techniques that can minimize the time and deviations associated with different instrumental and process parameters. To meet this requirement, some new and more advanced analytical techniques have recently been discovered, like ultrasonic attenuation technique, BET technique, biosensors, etc. Conclusion: The present overview certifies the significance of different analytical techniques utilized in the nanosizing process. The overview also provides information on various patents related to sophisticated analytical tools that can meet the needs of such an advanced field. The data show that the nanotechnology field will flourish in the coming future.

New Insights into Pharmaceutical Nanocrystals for the Improved Topical Delivery of Therapeutics in Various Skin Disorders.

Nanotechnology has provided nanostructure-based delivery of drugs, among which nanocrystals have been investigated and explored for feasible topical drug delivery. Nanocrystals are nano-sized colloidal carriers, considered pure solid particles with a maximum drug load and a very small amount of stabilizer. The size or mean diameter of the nanocrystals is less than 1 µm and has a crystalline character. Prominent synthesis methods include the utilization of microfluidic- driven platforms as well as the milling approach, which is both adaptable and adjustable. Nanocrystals have shown a high capacity for loading drugs, utilization of negligible amounts of excipients, greater chemical stability, lower toxic effects, and ease of scale-up, as well as manufacturing. They have gained interest as drug delivery platforms, and the significantly large surface area of the skin makes it a potential approach for topical therapeutic formulations for different skin disorders including fungal and bacterial infections, psoriasis, wound healing, and skin cancers, etc. This article explores the preparation techniques, applications, and recent patents of nanocrystals for treating various skin conditions.

Nanoformulations Insights: A Novel Paradigm for Antifungal Therapies and Future Perspectives.

Currently, fungal infections are becoming more prevalent worldwide. Subsequently, many antifungal agents are available to cure diseases like pemphigus, athlete's foot, acne, psoriasis, hyperpigmentation, albinism, and skin cancer. Still, they fall short due to pitfalls in physiochemical properties. Conventional medications like lotion, creams, ointments, poultices, and gels are available for antifungal therapy but present many shortcomings. They are associated with drug retention and poor penetration problems, resulting in drug resistance, hypersensitivity, and diminished efficacy. On the contrary, nanoformulations have gained tremendous potential in overcoming the drawbacks of conventional delivery. Furthermore, the potential breakthroughs of nanoformulations are site-specific targeting. It has improved bioavailability, patient-tailored approach, reduced drug retention and hypersensitivity, and improved skin penetration. Nowadays, nanoformulations are gaining popularity for antifungal therapy against superficial skin infections. Nanoformulations-based liposomes, niosomes, nanosponges, solid lipid nanoparticles, and potential applications have been explored for antifungal therapy due to enhanced activity and reduced toxicity. Researchers are now more focused on developing patient-oriented target-based nano delivery to cover the lacunas of conventional treatment with higher immune stimulatory effects. Future direction involves the construction of novel nanotherapeutic devices, nanorobotics, and robust methods. In addition, for the preparations of nanoformulations for clinical studies, animal modeling solves the problems of antifungal therapy. This review describes insights into various superficial fungal skin infections and their potential applications, nanocarrier-based drug delivery, and mechanism of action. In addition, it focuses on regulatory considerations, pharmacokinetic and pharmacodynamic studies, clinical trials, patents, challenges, and future inputs for researchers to improve antifungal therapy.

Herbal Medicines - a Fruitful Approach to Periodic Illness Dysmenorrhoea: Evidence-based Review.

Dysmenorrhea (menstrual or periodic pain) is a discomfort that occurs during painful periods. It is the first and most prominent reason for female lower abdominal pain. Most adolescent girls consider it a curse due to the periodic occurrence of painful cramps and bleeding. The pathogenesis of painful periods is most likely because of increased prostanoids, notably prostaglandins, produced by the cyclooxygenase pathway (PGs). Misuse of synthetic medications leads to the development of medication resistance and deposits toxic residues in the body; thus, there is a critical need for safe and effective alternatives. In recent decades, herbal treatment approaches have found extensive applications in the treatment of various ailments. Herbal therapies are an alternate source, which include several bioactive chemicals, and recent improvements in our understanding of the value of herbal therapy methods have caused a sharp rise in their production. The main focus of this review was to study herbal treatment options; the recent studies conducted on herbal therapies and various experimental investigations on dysmenorrhea and herbal therapy methods have been studied, and randomized controlled trials and animal models have been discussed describing the anti-inflammatory properties of some potential herbal medicines that can be used as treatment options for dysmenorrhoea. This review aimed to present herbal treatments that can be used as alternative traditional synthetic medications and oral hormonal contraceptives in the treatment of painful menstruation.

Design, Fabrication and Characterization of Esomeprazole Nanocrystals for Enhancing the Dissolution Rate and Stability.

BACKGROUND: Poor solubility and low dissolution rate limit the work at poorly water-soluble drugs like Esomeprazole. To overcome this problem, different technologies had to be used but could not resolve the problem, significantly. The main aim of this patent study was to prepare the nanocrystals using the evaporative precipitation ultrasonication method in order to improve the dissolution rate and stability of Esomeprazole (ESM). METHODS: For obtaining the nanocrystals, different nanoformulations were prepared using the pluronic F-68 in different concentrations, and then the screened formulation was lyophilized in the presence of two distinct cryoprotectants; mannitol and sucrose. The obtained nanocrystals were characterized for their re-dispersibility, crystalline state, dissolution behavior, particle size, polydispersibility index and morphology. Dissolution study of ESM nanocrystals was performed in a buffer solution of pH-7.4, and compared to that of bulk ESM sample and ESM/pluronic F-68 physical mixture. RESULTS: Cryoprotectant containing nanocrystals exhibit the re-dispersion in water after the manual shaking. 5% mannitol containing nanocrystals showed the least polydispersity index (0.42 ± 0.11) and narrowest particle size (186 ± 12.9 nm). The Powder X-ray Diffraction (PXRD) pattern and differential scanning calorimeter (DSC) thermograms revealed that the crystalline state of the drug was not changed after the different physical treatment. Freeze-dried nanocrystals showed a faster dissolution rate and almost 99.45% of the drug was released within 60 min. However, the bulk drug and a physical mixture of bulk drug/pluronic F-68 showed only 22.65% and 21.3% of drug release, respectively, after 60 min. This paper reviews the related patents on Esomeprazole Nanocrystals. CONCLUSION: The different findings revealed that nanocrystals could be a potential alternate for solving the dissolution rate and stability issue of ESM like poorly soluble drugs.

Self-Emulsifying Drug Delivery System (SEDDS): An Emerging Dosage Form to Improve the Bioavailability of Poorly Absorbed Drugs.

The main objective of drug(s) formulation is to enhance the bioavailability of the drug within the body. Some of the challenging issues associated with poorly water-soluble drugs concern solubility and bioavailability factors. To overcome these problems, new technologies, such as lipid-based drug delivery systems including micro or nano emulsifying drug delivery system, have gained importance in recent years, due to their enhanced solubility and bioavailability in the gastrointestinal tract. Such systems are incorporated or solubilized within the lipid excipients or mixed with oils or surfactants/co-solvents to facilitate the solubility and absorption rate, which can enhance the bioavailability of the targeted drug. This review provides a comprehensive summary about the properties, factors affecting formulations, excipients, formulation techniques, and characterization of self-emulsifying drug delivery systems. It also focuses on the new approaches concerned with SEDDS.

Carissa carandas L. - phyto-pharmacological review.

OBJECTIVES: Carissa carandas is an evergreen thorny shrub (Apocynaceae family), commonly, known as karonda. It has small berry-shaped fruits, used as additive in many pickles or as a spice in northern India. METHODS: The present review covers the literature survey from 1968 to 2020. The data have been collected from various journals, books, thesis and some of the electronic search via Internet-based information such as PubMed, Google Scholar, ScienceDirect, EBSCO, online electronic journals, SpringerLink, Wiley and Ayush. KEY FINDINGS: From literature survey, it has been found that the herbal drug contains wide variety of flavonoids, phenolic acids, steroids, volatile oils, lignans, alkaloids, polysaccharides and so on. These phytochemicals exhibit a range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antimicrobial and antifungal properties. CONCLUSIONS: This current review offers primary data for further research work. The in-vitro evaluations as well as in-vivo models/experiments have provided a biosynthetic observation for its various ethno-pharmacological uses and even pharmacological properties. This review would provide all valuable information which will be beneficiary to conduct some important pharmacokinetic and toxicological research works on human models with respect to ensure the effects of active ingredients in the body and even to validate its safety issues in clinical aspects.

Patented and Approval Scenario of Nanopharmaceuticals with Relevancy to Biomedical Application, Manufacturing Procedure and Safety Aspects.

BACKGROUND: Nanopharmaceutical is the field that arises gradually but many challenges are also still there. This review aims to identify these challenges and give the focus on their rectification. METHODS: In this paper, we memorize the safety issues, patented manufacturing procedure, applications and regulatory aspects of the nanopharmaceuticals by using the peer-reviewed research literatures. All the screened literatures described the quality content of nanopharmaceuticals with relevancy to biomedical and pharmaceutical field. RESULTS: Nanopharmaceuticals have great potential to resolve the different issues such as; site specific drug delivery however, many challenges are also arising in their commercialization. In the recent years, some nanopharmaceuticals have the desired quality and safety for the public, have been approved by the regulatory agencies but this field is still a thrust area that demands a lot of attention. CONCLUSION: The present review article confirms the importance of nanopharmaceuticals and impart the knowledge for making the significant approaches and strategies to overcome the manufacturing, safety, legal and regulatory issues related to nanopharmaceuticals.

Development of ibuprofen nanoliposome for transdermal delivery: Physical characterization, in vitro/in vivo studies, and anti-inflammatory activity.

OBJECTIVE: Ibuprofen is an established non-steroidal anti-inflammatory drug commonly used for general inflammation. However, it causes gastrointestinal troubles when administered orally, thereby decreasing patient compliance. Transdermal application of vesicular formulation of Ibuprofen will provide better patient compliance and efficacy. METHODS: Six different compositions of lipid constituents have been formulated into nanovesicles using thin-film hydration method and dispersed into gel using Carbopol 934. The formulations were characterized based on physicochemical parameters using photon correlation spectroscopy, transmission electron microscopy, in vitro drug release, ex vivo skin permeation using human skin, and in vivo studies. RESULTS: The formulation, ibuprofen liposomal gel-5 (ILG-5), had nanoliposome of smallest size (159 nm) and polydispersity index (0.331). This formulation showed moderate zeta potential and the highest encapsulation. All the formulations including IG showed a considerable amount of drug release through in vitro synthetic membrane. ILG-5 showed maximum permeation during skin permeation studies. IG showed no permeation in ex vivo settings. ILG-5 has shown the highest Cmax and AUC during in vivo permeation study. CONCLUSIONS: The present work clearly shows the superiority of nanoliposome formulation over non-vesicular formulations and that lipid composition containing 7/3/1 molar ratio of phosphatidylcholine, cholesterol, and dicetyl phosphate is optimum for nanoliposome preparations, in the cases where controlled delivery of drug is needed for a sufficient period of time.

Nanosuspension Technology For Poorly Soluble Drugs: Recent Researches, Advances and Patents.

Nowadays, in pharmaceutical industries, the attention on nanosized materials is growing gradually due to their wide applications in drug delivery systems. Recently, out of different nanosize systems, nanosuspension system has undergone a lot of interest in such a way to rectify the solubility and bioavailability problem due to their technical simplicity and cost-effectiveness property compared to other colloidal systems. Nanosuspension technology has proven that it can be a superior substitute over alternative approaches, which are available for enhancing the bioavailability of different drugs having low solubility. Since today, nanosuspensions have been greatly evolved for a huge number of drugs and also investigated for their potential applications. The various unique features make the nanosuspension to enable their utilization in numerous dosage forms and given through different routes, including parenteral, oral, topical, peroral, ocular and pulmonary routes. A large number of products grounded in nanosuspension technology are present in the market, and some are on the way. In fact, the number of such types of products is much more in comparison of other nanotechnologies based products. Additionally, the different preparation methods used to prepare the nanosuspensions are also well- established and patented. This article reviews the recent research, advances in formulation and their approaches related to nanosuspensions with emphasis given on different patents related to nanosuspension methods.

Enhanced oral bioavailability of efavirenz by solid lipid nanoparticles: in vitro drug release and pharmacokinetics studies.

Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6-98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (C max) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES).

Plumbagin analogs-synthesis, characterization, and antitubercular activity.

Considering the emerging problem of drug resistance in tuberculosis, there is an urgent need of development of new analogs that are useful in curing drug resistant tuberculosis. In India, tuberculosis continues to remain one of the most pressing health problems. India is the highest tuberculosis burden country in the world, accounting one fifth of global incidence - estimated 2.0-2.5 million cases annually. In 2011, approximately 8.7 million new cases of tuberculosis and 1.4 million people die from tuberculosis each year worldwide. Current antitubercular therapies are successful against normal tuberculosis but it is not suitable for drug resistant tuberculosis. In this study Plumbagin analogs, obtained from Plumbago zeylanica (Family-Plumbaginaceae), have been synthesized. Out of the various synthesized analogs, the antitubercular activity of compound a and b was evaluated using standard H37Rv and S, H, R, and E sensitive M tuberculosis strains using LRF assay method. Compound a showed strong activity against both standard H37Rv and S, H, R and E sensitive M. tuberculosis strains as compared to standard Rifampicin. The other compounds are proved to be more active against standard H37Rv and S, H, R and E sensitive M. tuberculosis strain as compared to Rifampicin.

Formulation and evaluation of controlled-release of telmisartan microspheres: In vitro/in vivo study.

The aim of this work was to design a controlled-release drug-delivery system for the angiotensin-II receptor antagonist drug telmisartan. Telmisartan was encapsulated with different EUDRAGIT polymers by an emulsion solvent evaporation technique and the physicochemical properties of the formulations were characterized. Using a solvent evaporation method, white spherical microspheres with particle sizes of 629.9-792.1 µm were produced. The in vitro drug release was studied in three different pH media (pH 1.2 for 2 hours, pH 6.8 for 4 hours, and pH 7.4 for 18 hours). The formulations were then evaluated for their pharmacokinetic parameters. The entrapment efficiency of these microspheres was between 58.6% and 90.56%. The obtained microspheres showed good flow properties, which were evaluated in terms of angle of repose (15.29-26.32), bulk and tapped densities (0.37-0.53 and 0.43-0.64, respectively), Carr indices and Hausner ratio (12.94-19.14% and 1.14-1.23, respectively). No drug release was observed in the simulated gastric medium up to 2 hours; however, a change in pH from 1.2 to 6.8 increased the drug release. At pH 7.4, formulations with EUDRAGIT RS 100 showed a steady drug release. The microsphere formulation TMRS-3 (i.e., microspheres containing 2-mg telmisartan) gave the highest Cmax value (6.8641 µg/mL) at 6 hours, which was three times higher than Cmax for telmisartan oral suspension (TOS). Correspondingly, the area under the curve for TMRS-3 was 8.5 times higher than TOS. Particle size and drug release depended on the nature and content of polymer used. The drug release mechanism of the TMRS-3 formulation can be explained using the Higuchi model. The controlled release of drug from TMRS-3 also provides for higher plasma drug content and improved bioavailability.

Oral bioavailability and stability study of a self-emulsifying drug delivery system (SEDDS) of amphotericin B.

Amphotericin B (AmB) is a poorly water soluble polyene antifungal antibiotic which is negligibly absorbed from the gastro intestinal tract after oral administration. The objective of this research work was to study the oral bioavailability and stability of a self-emulsifying drug delivery system (SEDDS) of amphotericin B (AmB). The SEDDS formulation consisted of glyceryl monooleate, tween 80, polyethylene glycol 400 (PEG 400) and propylene glycol and had AmB content of about 8 mg per ml. The stability of the SEDDS formulation was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) in comparison to pure drug. Oral bioavailability of the SEDDS formulation was studied in rats in comparison to the pure drug. The formulation was filled in two different types of capsule shell, namely HPMC capsule and hard gelatin capsule and stability of the formulation was studied for 3 months. The SEDDS formulation resulted in a mean AUC value of 40.57µg/ml.hr with mean peak plasma concentration of 6.17µg/ml reached after 2 hours after oral administration in rats, whereas concentration of AmB in plasma was not detectable after administration of the pure drug. The formulation filled in hard gelatin capsule shell was physically and chemically stable for more than 3 months under refrigeration (4°C). The study demonstrates that SEDDS approach can be successfully utilized for oral delivery of AmB.

Novel micropelletization technique: highly improved dissolution, wettability and micromeritic behavior of domperidone.

The aim of the investigation is to improve the dissolution, wettability, and micromeritic behavior of domperidone, a dopamine antagonist, used in the treatment of nausea and vomiting. Micropelletization technique, a possible approach for ensuring maximum dissolution with enhanced wettability, and uniform pellet size almost spherical so as to achieve the smooth gastric transit of drug have been estimated. Micropellets were prepared utilizing solvent diffusion technique and all the process parameters such as solvent-non-solvent ratio, stirring speed, temperature, and effect of aggregating agent on the micropellets formulation have been optimized. The addition of an aggregating agent (10%v/v of isopropyl alcohol) improved the uniform micropellets formation and the method was reproducible. The micromeritic properties such as size distribution, surface property (using Scalar-USB digital photomicroscope), packability, and flowability of the formulated micropellets were characterized. Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetric (DSC) analysis were performed to explain the results. Formulated micropellets showed clear and highly improved in vivo dissolution behavior, probably due to high wettability. The micropelletized drug was stable at room temperature, 25 degrees C/60% relative humidity (RH), and 45 degrees C/70% RH, after 12 weeks.