In vitro profiling and molecular dynamics simulation studies of berberine loaded MCM-41 mesoporous silica nanoparticles to prevent neuronal apoptosis.

Neuronal loss in Alzheimer's disease has been reported to display features of apoptosis, pyroptosis (programmed necrosis), or necroptosis. This study thoroughly examines the production and characterization of MCM-41 based berberine (BBR)-loaded porous silica nanoparticles (MSNs) by a modified Stöber method, focusing on their possible role in inhibiting the apoptotic process. Particle size, polydispersity index, morphology, drug loading, zeta potential, entrapment efficiency, and drug release were examined. The formulation was analyzed using various spectroscopic techniques. The surface area was computed by the Brunauer-Emmett-Teller plot. Computational models were developed for molecular dynamics simulation studies. A small PDI value indicated an even distribution of particles at nanoscale sizes (80-100 nm). Results from XRD and SEAD experiments confirmed the amorphous nature of BBR in nanoparticles. Nanoparticles had high entrapment (75.21 ± 1.55%) and drug loading (28.16 ± 2.5%) efficiencies. A negative zeta potential value (-36.861.1 mV) indicates the presence of silanol groups on the surface of silica. AFM findings reveal bumps due to the surface drug that contributed to the improved roughness of the MSNs-BBR surface. Thermal gravimetric analysis confirmed the presence of BBR in MSNs. Drug release was controlled by simple diffusion or quasi-diffusion. Molecular dynamics simulations confirmed the existence of diffused drug molecules. Cellular studies using SH-SY-5Y cells revealed dose-dependent growth inhibition. Fragmented cell nuclei and nuclear apoptotic bodies in DAPI-stained cells exposed to nanoparticles showed an increase in apoptotic cells. Flow cytometry analysis demonstrated a lower red-to-green ratio in SH-SY-5Y cells treated with nanoparticles. This suggests improved mitochondrial health, cellular viability restoration, and prevention of the apoptotic process. This study provides essential data on the synthesis and potential of MSNs loaded with BBR, which may serve as a viable therapeutic intervention for conditions associated with apoptosis.

Types of memory, dementia, Alzheimer's disease, and their various pathological cascades as targets for potential pharmacological drugs.

Alzheimer's disease (AD) is the most common type of dementia accounting for 90% of cases; however, frontotemporal dementia, vascular dementia, etc. prevails only in a minority of populations. The term dementia is defined as loss of memory which further takes several other categories of memories like working memory, spatial memory, fear memory, and long-term, and short-term memory into consideration. In this review, these memories have critically been elaborated based on context, duration, events, appearance, intensity, etc. The most important part and purpose of the review is the various pathological cascades as well as molecular levels of targets of AD, which have extracellular amyloid plaques and intracellular hyperphosphorylated tau protein as major disease hallmarks. There is another phenomenon that either leads to or arises from the above-mentioned hallmarks, such as oxidative stress, mitochondrial dysfunction, neuroinflammation, cholinergic dysfunction, and insulin resistance. Several potential drugs like antioxidants, anti-inflammatory drugs, acetylcholinesterase inhibitors, insulin mimetics or sensitizers, etc. studied in various previous preclinical or clinical reports were put as having the capacity to act on these pathological targets. Additionally, agents directly or indirectly targeting amyloid and tau were also discussed. This could be further investigated in future research.

Cocos nucifera Husk Biomass as an Effective Adsorbent for Industrial Wastewater Removal: Harnessing the Power of Nature.

BACKGROUND: Rapid industrialization has polluted waterways, threatened aquatic ecosystems and endangered human health. To solve this problem, sustainable industrial practices and innovative water treatment technology must be implemented to ensure clean and safe water for future generations. METHODS: This study aimed to investigate the adsorbent capacity of Cocos nucifera husk for ineffective removal of methylene blue (MB), a cationic dye abundantly found in industrial effluent. Adsorption capacity is measured using parameters such as dye elimination percentage and polymer dosage. The Langmuir and Freundlich isotherms, adsorption kinetics (pseudo-first, pseudo-second, and second order), and intraparticle diffusion were determined to better understand the adsorption process. RESULTS: The increased dosage of cellulose fiber results in the availability of a greater number of adsorption sites and an increased surface area. However, the dye removal efficacy decreased after reaching a specific dosage of 0.6 g/L. A concentration of 0.05 g/L was most effective in eliminating Methylene blue (MB). The value of the separation factor (0.99) suggested a favorable adsorption isotherm. The reciprocal of the heterogeneity factor (-1.469) demonstrated the concentration-independent adsorption behavior of Fiber. Freundlich and Langmuir's isotherm model showed that the pseudo-second-order kinetic model demonstrated the highest level of correlation with the experimental data about the mechanism of adsorption. The Methylene blue (MB) adsorption is not limited by the intraparticle diffusion and adsorption is influenced by surface area and concentration variation of fiber as well as solvent concentration, as evidenced by low R2 value and the fact that the intraparticle diffusion plot does not intersect with the origin. CONCLUSION: The study concludes that Cocos nucifera husk can be effectively used for the treatment of wastewater.

Nanoliposomes Embedded Nanocochleates for Codelivery of Artemether and Lumefantrine: An In Vitro and In Vivo Study.

Antimalarial drugs are being encapsulated in nanotechnology-based carriers because there are not enough new treatment options and people are becoming more resistant to the ones that are already available. This approach uses two or more biochemical targets of malarial parasites. The codelivery of artemether and lumefantrine (AL) combines the synergistic effect of artemether for an early onset of action followed by the prolonged effect of lumefantrine. The bioavailability of artemether and lumefantrine is low due to their low solubility. Thus, an alternative lipidic formulation, namely nanocochleate, was developed for the selected drugs by adding calcium ions into preformed nanoliposomes (AL-loaded liposomes). Using phospholipon 90H and cholesterol, a thin-film hydration method produced drug-loaded liposomes. The synthesized AL-loaded liposomes were further incorporated into nanocochleates. The formulations were evaluated for in vitro and in vivo parameters. Nanocochleates had a particle size of 200.7 nm, a zeta potential of -9.4 mV, and an entrapment efficiency of 73.12% ± 1.82% and 61.46% ± 0.78%, respectively, for artemether and lumefantrine. Whereas liposomes had a particle size of 210 nm and an entrapment efficiency of 67.34% ± 1.52% and 53.24% ± 0.78%, respectively, for artemether and lumefantrine. An X-ray diffraction study confirmed the amorphous state of artemether and lumefantrine in liposomes and nanocochleate. Nanocochleate showed a controlled release profile for loaded drugs. When compared with free drugs, nanocochleate showed low tissue distribution and a 20-fold increase in bioavailability in rats. Thus, nanocochleate offers an interesting alternative to an existing dosage form for the treatment of malaria.

Disease X: Beyond Fear, Toward Preparedness.

In recent years, there has been a growing concern regarding the increasing incidence of infectious diseases with potential global transmission [1]. The World Health Organization (WHO) coined the phrase "Disease X" to denote a theoretical infectious disease that has not yet been detected but has the capacity to cause a global pandemic. Disease X denotes an unidentified pathogenic agent with the potential to instigate a forthcoming global outbreak [2]. Commencing with a convened gathering on the 18th of November 2022, the WHO has initiated a comprehensive assembly of more than 300 esteemed experts. The primary objective of this assembly is to meticulously examine the available information pertaining to over 25 virus families, bacteria, and a hypothetical pathogen referred to as "Disease X." The initial publication of the list occurred in 2017.

Non-coding RNAs in Regulation of Protein Aggregation and Clearance Pathways: Current Perspectives Towards Alzheimer's Research and Therapy.

Alzheimer's disease (AD) is the leading cause of dementia, affecting approximately 45.0 million people worldwide and ranking as the fifth leading cause of mortality. AD is identified by neurofibrillary tangles (NFTs), which include abnormally phosphorylated tau-protein and amyloid protein (amyloid plaques). Peptide dysregulation is caused by an imbalance between the production and clearance of the amyloid-beta (Aß) and NFT. AD begins to develop when these peptides are not cleared from the body. As a result, understanding the processes that control both normal and pathological protein recycling in neuronal cells is critical. Insufficient Aß and NFT clearance are important factors in the development of AD. Autophagy, lysosomal dysfunction, and ubiquitin-proteasome dysfunction have potential roles in the pathogenesis of many neurodegenerative disorders, particularly in AD. Modulation of these pathways may provide a novel treatment strategy for AD. Non-coding RNAs (ncRNAs) have recently emerged as important biological regulators, with particular relevance to the emergence and development of neurodegenerative disorders such as AD. ncRNAs can be used as potential therapeutic targets and diagnostic biomarkers due to their critical regulatory functions in several biological processes involved in disease development, such as the aggregation and accumulation of Aß and NFT. It is evident that ncRNAs play a role in the pathophysiology of AD. In this communication, we explored the link between ncRNAs and AD and their regulatory mechanisms that may help in finding new therapeutic targets and AD medications.

Sorafenib tosylate-loaded nanosuspension: preparation, optimization, and in vitro cytotoxicity study against human HepG2 carcinoma cells.

This study aimed to optimize nanosuspension of sorafenib tosylate (an anticancer hydrophobic drug molecule) using a central composite design. Nanosuspension was prepared using a nanoprecipitation-ultrasonication approach. FTIR and DSC analyses demonstrated that the drug and excipients were physicochemically compatible. X-ray powder diffraction analysis confirmed amorphous form of the payload in the formulation. The optimized formulation (batch NSS6) had a zeta potential of -18.1 mV, a polydispersity of 0.302, and a particle size of 97.11 nm. SEM analysis confirmed formation of rod-shaped particles. After 24 h, about 64.45% and 86.37% of the sorafenib tosylate was released in pH 6.8 and pH 1.2, respectively. The MTT assay was performed on HepG2 cell lines. IC50 value of the optimized batch was 39.4 µg/mL. The study concluded that sorafenib tosylate nanosuspension could be a promising approach in the treatment of hepatocellular cancer.

Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment.

When breast cells divide and multiply out of control, it is called breast cancer. Symptoms include lump formation in the breast, a change in the texture or color of the breast, or a discharge from the nipple. Local or systemic therapy is frequently used to treat breast cancer. Surgical and radiation procedures limited to the affected area are examples of local management. There has been significant worldwide progress in the development of monoclonal antibodies (mAbs) since 1986, when the first therapeutic mAb, Orthoclone OKT3, became commercially available. mAbs can resist the expansion of cancer cells by inducing the destruction of cellular membranes, blocking immune system inhibitors, and preventing the formation of new blood vessels. mAbs can also target growth factor receptors. Understanding the molecular pathways involved in tumor growth and its microenvironment is crucial for developing effective targeted cancer therapeutics. Due to their unique properties, mAbs have a wide range of clinical applications. Antibody-drug conjugates (ADCs) are drugs that improve the therapeutic index by combining an antigen-specific antibody with a payload. This review focuses on the therapeutic applications, mechanistic insights, characteristics, safety aspects, and adverse events of mAbs like trastuzumab, bevacizumab, pertuzumab, ertumaxomab, and atezolizumab in breast cancer treatment. The creation of novel technologies utilizing modified antibodies, such as fragments, conjugates, and multispecific antibodies, must be a central focus of future studies. This review will help scientists working on developing mAbs to treat cancers more effectively.

Chitosan based sorafenib tosylate loaded magnetic nanoparticles: Formulation and in-vitro characterization.

Biocompatible magnetic nanoparticles are used for various biomedical applications. This study reported the development of nanoparticles with magnetic properties by embedding magnetite particles in the drug-loaded, crosslinked matrix of chitosan. Sorafenib tosylate-loaded magnetic nanoparticles were prepared by a modified ionic-gelation method. Particle size, zeta potential, polydispersity index, and entrapment efficiency of nanoparticles were in the range of 95.6 ± 3.4 nm to 440.9 ± 7.3 nm, 12.8 ± 0.8 mV to 27.3 ± 1.1 mV, 0.289 ± 0.011 to 0.571 ± 0.011, and 54.36 ± 1.26 % to 79.67 ± 1.40 %, respectively. The XRD spectrum of formulation CMP-5 confirmed the amorphous nature of the loaded drug in nanoparticles. TEM image confirmed the spherical shape of nanoparticles. Atomic force microscopic image of formulation CMP-5 indicated a mean surface roughness of 10.3597 nm. The magnetization saturation of formulation CMP-5 was 24.74 emu/g. Electron paramagnetic resonance spectroscopy revealed that formulation CMP-5's g-Lande's factor was 4.27, which was extremely near to the 4.30 (usual for Fe3+ ions). Residual paramagnetic Fe3+ ions may be responsible for paramagnetic origin. The data suggests superparamagnetic nature of particles. Formulations released 28.66 ± 1.22 % to 53.24 ± 1.95 % and 70.13 ± 1.72 % to 92.48 ± 1.32 % of the loaded drug after 24 h in pH 6.8 and pH 1.2, respectively. The IC50 value of formulation CMP-5 was 54.75 µg/mL in HepG2 (human hepatocellular carcinoma cell lines).

Bioinspired microrobots: Opportunities and challenges in targeted cancer therapy.

Chemotherapy is still the most effective technique to treat many forms of cancer. However, it also carries a high risk of side effects. Numerous nanomedicines have been developed to avoid unintended consequences and significant negative effects of conventional therapies. Achieving targeted drug delivery also has several challenges. In this context, the development of microrobots is receiving considerable attention of formulation scientists and clinicians to overcome such challenges. Due to their mobility, microrobots can infiltrate tissues and reach tumor sites more quickly. Different types of microrobots, like custom-made moving bacteria, microengines powered by small bubbles, and hybrid spermbots, can be designed with complex features that are best for precise targeting of a wide range of cancers. In this review, we mainly focus on the idea of how microrobots can quickly target cancer cells and discuss specific advantages of microrobots. A brief summary of the microrobots' drug loading and release behavior is provided in this manuscript. This manuscript will assist clinicians and other medical professionals in diagnosing and treating cancer without surgery.

Preparation and Optimization of Liposome Containing Thermosensitive In Situ Nasal Hydrogel System for Brain Delivery of Sumatriptan Succinate.

Drug absorption is improved by the intranasal route's wide surface area and avoidance of first-pass metabolism. For the treatment of central nervous system diseases such as migraine, intranasal administration delivers the medication to the brain. The study's purpose was to develop an in situ nasal hydrogel that contained liposomes that were loaded with sumatriptan succinate (SS). A thin-film hydration approach was used to create liposomes, and a 32 factorial design was used to optimize them. The optimized liposomes had a spherical shape, a 171.31 nm particle size, a high drug encapsulation efficiency of 83.54%, and an 8-h drug release of 86.11%. To achieve in situ gel formation, SS-loaded liposomes were added to the liquid gelling system of poloxamer-407, poloxamer-188, and sodium alginate. The final product was tested for mucoadhesive strength, viscosity, drug content, gelation temperature, and gelation time. Following intranasal delivery, in vivo pharmacokinetic investigations showed a significant therapeutic concentration of the medication in the brain with a Cmax value of 167 ± 78 ng/mL and an area under the curve value of 502 ± 63 ng/min·mL. For SS-loaded liposomal thermosensitive nasal hydrogel, significantly higher values of the nose-to-brain targeting parameters, that is, drug targeting index (2.61) and nose-to-brain drug direct transport (57.01%), confirmed drug targeting to the brain through the nasal route. Liposomes containing thermosensitive in situ hydrogel demonstrated potential for intranasal administration of SS.

Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats.

OBJECTIVES: Vascular dementia (VaD), being strongly associated with metabolic conditions is a major health concern around the world. Diabetes is a major risk factor for the development of VaD. This study investigates the efficacy of quercetin and folacin in diabetes induced vascular endothelium dysfunction and related dementia. METHODS: Single dose streptozotocin (STZ) (50 mg/kg i.p) was administered to albino Wistar rats (male, 200-250 g) by dissolving in citrate buffer. Morris water maze (MWM) and attentional set shifting tests were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), mitochondrial enzyme complex (I, II, and IV), inflammatory markers (interleukin-IL-6, IL-10, tumor necrosis factor-TNF-α, and myeloperoxidase-MPO), and acetylcholinesterase activity-AChE were also assessed. Quercetin (30 mg kg-1/60 mg kg-1) and folacin (30 mg kg-1/60 mg kg-1) were used as the treatment drugs. Donepezil (0.5 mg kg-1) was used as a positive control. RESULTS: STZ administered rats showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in brains' oxidative stress; inflammation; AChE activity, and decrease in mitochondrial complex (I, II, and IV) activity. Administration of quercetin and folacin in two different doses, significantly attenuated the STZ induced diabetes induced impairments in the behavioral, endothelial, and biochemical parameters. CONCLUSIONS: STZ administration caused diabetes and VaD which was attenuated by the administration of quercetin and folacin. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced VaD conditions.

Nanovaccine: A Hope to Triumph the Battle Against Novel Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. METHODS: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. RESULTS: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/subunit protein vaccines, peptide vaccines, virus-like particles, etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into patent clinical trials. CONCLUSION: Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

Intranasally Co-administered Berberine and Curcumin Loaded in Transfersomal Vesicles Improved Inhibition of Amyloid Formation and BACE-1.

Selective permeability of the blood-brain barrier restricts the treatment efficacy of neurologic diseases. Berberine (BBR) and curcumin (CUR)-loaded transferosomes (TRANS) were prepared for the effective management of Alzheimer's disease (AD). The study involved the syntheses of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS by the film hydration method. Vesicles were characterized to ensure the formation of drug-loaded vesicles and their in vivo performance. The particle sizes of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS were 139.2 ± 7, 143.4 ± 8, and 165.3 ± 6.5 nm, respectively. The presence of diffused rings in the SED image indicates the crystalline nature of the payload. Low surface roughness in an AFM image could be associated with the presence of a surface lipid. BBR-CUR-TRANS showed 41.03 ± 1.22 and 47.79 ± 3.67% release of BBR and 19.22 ± 1.47 and 24.67 ± 1.94% release of CUR, respectively, in phosphate buffer saline (pH 7.4) and acetate buffer (pH 4.0). Formulations showed sustained release of both loaded drugs. BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS exhibited a lower percentage of hemolysis than pure BBR and CUR, indicating the safety of the payload from delivery vesicles. Lower percentages of binding were recorded from BBR-CUR-TRANS than BBR-TRANS and CUR-TRANS. Acetylcholinesterase inhibition activity of the prepared transferosomes was greater than that of pure drugs, which are thought to have good cellular penetration. The spatial memory was improved in treated mice models. The level of malondialdehyde decreased in AD animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS, respectively, as compared to the scopolamine-induced AD animals. BBR-CUR-TRANS-treated animals showed the highest decrease in the NO level. The catalase level was significantly restored in scopolamine-intoxicated animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS. The immunohistochemistry result suggested that the BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS have significantly decreased the regulation of expression of BACE-1 through antioxidant activity. In conclusion, the study highlights the utility of formulated transferosomes as promising carriers for the co-delivery of drugs to the brain.

Bioelectronic medicines: Therapeutic potential and advancements in next-generation cancer therapy.

Bioelectronic medicine has tremendous potential in biomedical sector including oncology research, research on biomechanical and chemical properties of cells and biomaterials, healing bone tissue using electromagnetic fields, and understanding bioelectrical properties of aging. Bioelectronic medicine uses electricity to alter the body's electrical communication systems in order to treat various illnesses. The bioelectric circuits produce an endogenous electric field and a resting voltage when the cells are functioning and communicating. Oncology research has gained considerable interest focused on the development of emerging bioelectric cancer medicines. Reprogrammable circuits that underlie cancer, regeneration, and embryogenesis are known as bioelectric signalling. It is possible to create new therapeutic options to slow the spread of cancer by taking advantage of the bioelectric properties of cancer cells. The treatment of cancer may benefit from bioelectronic medicine. We looked into the value of bioelectrical energy in the fight against disease. This communication also covered the methods for therapeutically controlling this fatal illness. It is crucial to identify or measure the electrical activity of body cells in order to control or modify bioelectricity and bring about changes in cell structure. Knowledge of the cell-to-cell ionic interaction, faradaic processes, and their function in developing cancer phenotypes may improve cancer treatment approaches. With new evidence supporting an electrical mechanism that promotes this phenomenon, the data may also help us understand cancer metastasis better.

Genetic Causes of Alzheimer's Disease and the Neuroprotective Role of Melatonin in its Management.

Dementia is a global health concern owing to its complexity, which also poses a great challenge to pharmaceutical scientists and neuroscientists. The global dementia prevalence is approximately 47 million, which may increase by three times by 2050. Alzheimer's disease (AD) is the most common cause of dementia. AD is a severe age-related neurodegenerative disorder characterized by short-term memory loss, aphasia, mood imbalance, and executive function. The etiology of AD is still unknown, and the exact origin of the disease is still under investigation. Aggregation of Amyloid ß (Aß) plaques or neurotoxic Aßo oligomers outside the neuron is the most common cause of AD development. Amyloid precursor protein (APP) processing by ß secretase and γ secretase produces abnormal Aß monomers. This aggregation of Aß and NFT is promoted by various genes like BACE1, ADAM10, PIN1, GSK-3, APOE, PPARα, etc. Identification of these genes can discover several therapeutic targets that can be useful in studying pathogenesis and underlying treatments. Melatonin modulates the activities of these genes, thereby reducing Aß production and increasing its clearance. Melatonin also reduces the expression of APP by attenuating cAMP, thereby enhancing the non-amyloidogenic process. Present communication explored and discussed the neuroprotective role of melatonin against Aß-dependent AD pathogenesis. The manuscript also discussed potential molecular and genetic mechanisms of melatonin in the production and clearance of Aß that could ameliorate neurotoxicity.

Hydrogels for localized drug delivery: A special emphasis on dermatologic applications.

Skin disease treatment is a complex and time-consuming process due to the complex etiology, numerous side effects of conventional therapies, and difficulties in determining primary causes of the disease. Superficial wounds are often easy to treat. However, treatment of severe wounds caused by burn is challenging for clinicians. Optimum therapeutic benefits are based on the site-specific delivery of medicaments at the right time for a prolonged duration. Systemic toxicity and frequent dosing are the major challenges associated with the use of conventional therapeutics. Hydrogels are material of choice for drug delivery because of their high biocompatibility and ability to hold and release therapeutic agents. The number of hydrogels available for use in cosmetology and dermatology continues to grow during the past 1-2 decades. However, new hydrogel materials with high biocompatibility, antibacterial properties, and the ability to stimulate skin regeneration processes are in high demand. These are three-dimensional networks, which absorb a large amount of biological fluids and water. Hydrogels can be used as a biosensor, carrier systems for cells, drug delivery carriers especially for topical applications and in contact lenses. Hydrogels are highly porous carriers containing about 90% water. Stimuli-responsive hydrogels cause a change in network structure that is completely reversible in nature. The present review describes the applications of hydrogels in pharmaceutical formulations with a special emphasis on the treatment of dermatologic conditions such as acne, psoriasis, and mycosis.

Evolution of Solid Dispersion Technology: Solubility Enhancement Using Hydroxypropyl Methylcellulose Acetate Succinate: Myth or Reality?

Poorly aqueous soluble active pharmaceutical ingredients are highly risky development candidates and remain a concern of pharmaceutical industries in drug discovery and development processes. Pharmaceutical industries are putting significant efforts into the target identification and lead candidate development using combinatorial chemistry. About 40% of compounds arising from combinatorial screening are poorly water soluble. Pharmaceutical industries evolved over this challenge by coming up with reproducible and scalable particle size reduction or by identifying alternate morphs. Another important area where pharmaceutical industries are working is solid dispersion technology. With the emergence of the hot-melt extrusion and spray drying approach, many molecules have been brought to the market using solid dispersion technology from the discovery phase by improving bioavailability and thereby efficacy. Although the solid solution technology in the last 60 years evolved from eutectic mixtures, solid dispersions using water-soluble polymers, and enteric polymers especially hydroxypropyl methylcellulose acetate succinate (HPMCAS), still there is no preformulation tool to identify correct polymer or polymer combination at the early stage of development. Thus, this leads to the urgent need to focus on the design and development of third-generation solid dispersions for the unmet needs of the industries and society.