Pharmaceutical Science: New Insights and Developments Vol. 5

Bortezomib is indicated for single-agent use in the treatment of patients with multiple myeloma who have received at least two prior therapies and are progressing on their most recent therapy. Clinical investigations are underway to evaluate the safety and efficacy of Bortezomib alone or in combination with chemotherapy in multiple Myeloma, both at relapse and presentation, as well as in other cancer types. A Novel, rapid, precise, economical, and Accurate HPLC method for estimation of Bortezomib in bulk and formulations was developed and validated. Quantitative HPLC was performed on a binary gradient HPLC with Shimadzu LC20AT and LC20AT VP series HPLC pumps, with a 20\(\mu\)l injection of sample loop (manual), and SPD20 A VP UV–visible Detector. The Chromatographic resolution of Bortezomib was achieved using Acetonitrile: 0.1M Ammonium phosphate (acetic acid) Buffer, (60:40 V/V) as a mobile phase, UV detection at 230 nm, and BDS Hypersil C8 column flow rate 1ml/min. the extraction Recovery of Bortezomib from its formulation dosage form (tablets) was >99.59%, and the calibration curve was linear (r² = 0.999) over Bortezomib concentration ranging from 20 to 120 \(\mu\)g/ml. the method has an accuracy of > 99% and LOD and LOQ of 0.51900 \(\mu\)g /ml and 2.43450 \(\mu\)g/ml, respectively. A result of the present method was validated statistically and by recovery studies, which were found to be satisfactory. This linearity range covers all the strengths of Bortezomib, hence this can be conveniently used in the pharmaceutical manufacturing and formulation environment.

The whole plant of Kigelia africana (Lam.) Benth. belongs to the Bignoniaceae family and is widely cultivated throughout tropical and subtropical regions of the world, mainly in India and South Africa. Herbal medicine has gained significant global importance due to its medicinal properties and economic value. These herbal medicines have increased; their quality, safety, and efficiency are serious concerns in industrialized and developing countries. The kigelia plant is easily available at river banks and woodlands. The present research has been undertaken with the aim of formulating and evaluating the herbal gel containing Kigelia africana (Lam.) Benth., fruit extract. The Kigelia africana (Lam.) Benth., fruit extract contains Alkaloids, Saponins, Glycosides, Carbohydrates, Tannins, Flavonoids, Proteins, Terpenoids, and Fats. The gel formulation was developed by using Carbopol 940, Kigelia africana (Lam.) Benth., fruit extract, propylene glycol, methyl paraben, propyl paraben, and the required amount of distilled water. The skin pH (6.8-7.1) was maintained by dropwise addition of Triethanolamine. The physicochemical Parameters of formulations (pH, spreadability, Stability, etc.) were determined. Stability studies have been carried out as per ICH guidelines for 3 months at different temperatures and humidity. The results showed that the formulation containing 5% Kigelia africana (Lam.) Benth., fruit extract shows better stability. Further formulations have been studied for skin irritation on the animal model (Rat), and results showed that there was no skin irritation in animals. In conclusion, the studies revealed that the developed single herbal formulation consisting of 5% Kigelia africana (Lam.) Benth., extract comparatively better than the other formulations, but all the formulations were non-irritant and did not show any skin toxicity when applied daily for 7 days in rats. Its antibacterial and antifungal property was not under taken for any scientific study with herbal gel.

1,3,4-thiadazoles have become an important class of heterocycles and a great interest of researches because of their broad types of biological activity. The 1,3,4-thiadiazole ring's exceptional flexibility and wide range of therapeutic activity have made it an intriguing pharmacophore. This study clarifies the inherent characteristics of this five-membered heterocycle, emphasizing its polar and aromatic nature as well as its adaptability to changes that optimise its biological effect.  The broad spectrum of pharmacological action that 1,3,4-thiadiazole compounds display, including antimicrobial, antifungal, antiviral, anticancer, and anti-inflammatory effects was discussed. In this study, the maximal electroshock (MES) model was employed to evaluate the anticonvulsant potential of thiadiazole-based compounds, while their antiviral efficacy was assessed using the Tobacco Mosaic Virus (TMV) model. Numerous studies have also demonstrated the anticancer, anti-inflammatory, antifungal, antiviral, antibacterial, anticonvulsant, and antiparasitic properties of molecules having thiadiazole rings. Additionally, this study highlights the enormous potential for developing targeted medicines with improved effectiveness and selectivity and examines the intriguing possibilities of this flexible framework in the next drug discovery and development. Overall, this analysis highlights how important 1,3,4-thiadiazole is as a flexible pharmacophore that has the potential to completely change the field of medicine.

Background: Several novel technologies for oral drug delivery have recently become available to address the physicochemical and pharmacokinetic characteristics of drugs, while improving patient compliance. The basic disadvantage of conventional tablets is the high first-pass metabolism, which can be overcome by designing fast dissolving tablets (FDT).

Objective: The limited oral bioavailability of Levocetirizine Dihydrochloride, primarily due to its extensive first-pass metabolism, necessitated the development of fast-dissolving tablets that rapidly disintegrate in the oral cavity.

Methods: Fast-dissolving tablets containing 5 mg of Levocetirizine Dihydrochloride were formulated using the direct compression method with three synthetic super disintegrants in varying concentrations. Tablet thickness, Hardness Test, Friability Test, etc., were done for evaluation. Three tablets from each formulation were randomly selected, and in vitro dispersion time was performed.  The formulation development was primarily influenced by the type and concentration of polymers and the physicochemical properties of the drug.

Results: FTIR analysis confirmed the compatibility of the polymers with the drug. Various evaluation parameters, including thickness, weight variation, hardness, friability, in vitro dispersion time, wetting time, water absorption ratio, drug content uniformity, and in vitro drug release, were assessed. The optimized formulation (PF-9) exhibited an in vitro drug release of 99.81% within 10 minutes, with an in vitro dispersion time of just 1 second.

Conclusion: Among all developed formulations, the one containing 2.5% croscarmellose sodium (PF-9) was identified as the most effective, demonstrating superior disintegration and drug release characteristics for Levocetirizine Dihydrochloride tablets.

In 2021, the Centers for Disease Control and Prevention prioritized vaccination for mentally ill individuals as psychiatric illness was added to the list of COVID-19 risk factors. Currently, there are very few studies on mRNA vaccine efficacy in patients with SPI in treatment with psychotropic drugs. The messenger RNA (mRNA) vaccines for COVID-19, Pfizer-BioNTech and Moderna, were authorized in the US on an emergency basis in December of 2020. The rapid distribution of these therapeutics around the country and the world led to millions of people being vaccinated in a short time span, an action that decreased hospitalization and death but also heightened the concerns about adverse effects and drug-vaccine interactions.

Both psychotropic drugs, especially phenothiazines, and the COVID-19 mRNA vaccine enter cells via the endocytic pathway and may compete for this ingress pathway.  In this chapter, the modified mRNA therapeutics through the endocytic labyrinth and beyond, showing the events that must occur at each step to lead to the formation of neutralizing antibodies against the S(pike) protein, were followed.

The Vaccine Adverse Event Reporting System (VAERS) has gained additional attention during the COVID-19 pandemic, specifically regarding the rollout of mRNA therapeutics. However, for VAERS, the absence of a reporting platform for drug-vaccine interactions left these events poorly defined. For example, chemotherapy, anticonvulsants, and antimalarials were documented to interfere with the mRNA vaccines, but much less is known about the other drugs that could interact with these therapeutics, causing adverse events or decreased efficacy. In addition, SARS-CoV-2 exploitation of host cytochrome P450 enzymes, reported in COVID-19 critical illness, highlights viral interference with drug metabolism. For example, patients with severe psychiatric illness (SPI) in treatment with clozapine often displayed elevated drug levels, emphasizing drug-vaccine interaction. More studies are needed to assess the interaction between the major classes of psychotropic drugs, including antipsychotics, antidepressants, and mood stabilizers, with the mRNA therapeutics.

Aim: The present study investigated the effects of metformin (MET) in protection against oxidative stress and pancreatic damage using an animal model, to assess the effect of metformin on oxidative stress in vivo and in vitro.

Introduction: Diabetes mellitus is a worldwide health problem that has a deleterious impact on life expectancy and quality. People with diabetes have a higher oxidation state, which is detrimental to homeostasis. Numerous tissues have demonstrated the anti-oxidant qualities of metformin. An oral medication for diabetes called metformin aids in blood sugar regulation.

Methods: This study investigated the effect of metformin on total antioxidant markers in the serum and pancreatic tissue of Alloxan-induced diabetic rats. Diabetic rats were randomised into five groups for treatment and received metformin (100,200,300 mg/kg) orally once daily for four weeks. The antioxidant potential of evaluated total antioxidant status (TAOS) in vivo and through DPPH (1,1-diphenyl-2-picryl-hydrazyl) scavenging assay at 517 nm in vitro.

Results: A Considerable drop in elevated blood glucose level was observed in the alloxan-induced diabetic. At a dose of 100,200,300mg/kg demonstrated increase significantly improvement rate percentage in (M100, M200, M300) were (40.701 %),(48.063%) and (48.101%) respectively after end of treatment compared to diabetic group that decrease (-243.340%), TAOS were significantly increased in treated group than diabetic group" p= 0.000* ".The percentage of improvement rate elevation in treatment M100, M200, and M300 was (133.202 %,148.433% and 194.358%) respectively, compared with diabetic, while that percentage was decreased (-65.677%). Also, it improved pancreas histopathology compared to the diabetic control group it improved pancreas histopathology compared to the diabetic control group Antioxidant activity using DPPH was found to increase in a concentration-time-dependent manner IC₅₀ of metformin (498.0 µg/ml), while ascorbic acid IC₅₀ (µg/ml 29.62).

Conclusions: In "alloxan-induced diabetic rats", metformin provides "protective actions" against free radicals and oxidative stress, as well as improving pancreas tissue histology and lowering blood glucose levels.

Peptic ulcers are a category of disorders that manifest as a rupture in the intestinal epithelium that becomes saturated in acid and pepsin. It is the most frequent digestive tract disorder, with a global prevalence of 80% in developing and 40% in industrialised countries. The study aimed to compare the effectiveness and bioavailability using the in vitro dissolution method and assess other physicochemical properties of different brands of cimetidine tablets. Cimetidine is a model biopharmaceutics classification system (BCS) class-III medicine that is N-(amino sulfonyl)-3-[2 - [(diamine methylene) amino]-4-thiazolyl] methyl] thio] propanimidamide. It is a strong Histamine-2 (H2) receptor antagonist used in the treatment of peptic ulcers.

Five (5) different brands of cimetidine tablets, labelled A–E, were purchased and used for the analysis. Physicochemical tests such as weight uniformity, hardness, disintegration, friability, and dissolution test were conducted following standard British pharmacopoeia procedures. Samples A-E conformed to the weight uniformity standard with a mean % weight deviation of 0.37 – 1.39 %, while E had 11.52% based on the batch used. Samples B and A had the highest mean kgf (10.5 and 9.7), while sample E had the lowest kgf (4.4), hence liable to mechanical damage. All the samples used for the analysis had below 1.0% friability. All the samples passed the disintegration test, with sample A having the longest disintegration time (4.44 minutes) and sample C having the shortest disintegration time (0.21 minutes). At 25.99 minutes, Sample A had the fastest disintegration rate.

The method used in the analysis is accurate, precise, and cost-effective. The analysis does not require pretreatment of the drug and can compete with other existing methods in the routine quality control analysis of cimetidine in pharmaceutical formulation.

Treating wounds and their rapid healing is considered an important topic in ancient and modern research. The use of hydrogels is a promising strategy for achieving hemostasis and wound healing. Sol-gel synthesis is one of the methods for obtaining hydrogels. An innovative direction in sol-gel synthesis is the use of biogenic element polyolates (glycerolates) as biocompatible precursors with a wide range of pharmacological activity. It was shown that hydrogels based on silicon, iron, zinc, and boron glycerolates are non-toxic, and exhibit pronounced hemostatic activity, as well as antimicrobial activity, which is more pronounced for silicon-iron-zinc-boron and silicon-iron-boron glycerolate hydrogels. The results obtained indicate that these glycerolate hydrogels are potential hemostatic and antibiotic-independent antimicrobial agents for topical wound healing applications in medical and veterinary practice.

Centella asiatica (L.) Urban, also known as Gotu Kola, has been traditionally used in Asian medicine for wound healing, neurological disorders, and skin conditions. In recent years, emerging scientific evidence has illuminated its remarkable anticancer properties. This chapter provides a critical review of the phytochemical constituents of Centella asiatica, their underlying mechanisms of action in various cancer types, in vitro and in vivo experimental findings, and the challenges associated with clinical translation. Emphasis is placed on the herb’s molecular targets and potential synergism with conventional chemotherapeutic agents (James & Dubery, 2009).

Clitoria ternatea Linn (CT), a traditional Ayurvedic herb, has a longstanding history in traditional medicine. Modern studies now validate its efficacy in treating various neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and even stress-related disorders. Alzheimer’s disease (AD) is an age-related neurodegenerative disorder characterized by the irreversible loss of cognitive function, memory, and language impairment, and behavioral disturbances, which gradually become more severe. Medicinal plants are the backbone of modern medicines, and there is growing interest in discovering nootropic plants to combat cognitive dysfunction due to their less harmful effects. CT, is also known as ‘Aparjita/Butterfly pea’, has been used for centuries as a memory enhancer, antistress, anxiolytic, antidepressant, anticonvulsant, and antiulcer agent. These properties of CT raise the possibility of using it as a cholinesterase inhibitor in treating neurological disease symptoms. The preliminary phytochemical screening showed that the plant contained tannins, phlobatannin, carbohydrates, saponins, triterpenoids, phenols, flavanoids, flavonol glycosides, proteins, alkaloids, antharaquinone, anthocyanins, cardiac glycosides, Stigmast-4-ene-3, 6-dione, volatile oils and steroids. This review focused not only on available information about the neuropharmacological use of this plant but also its bioactive compounds, metabolites, and associated effects. It reviewed the existing knowledge to reveal the promising linkage of traditional medicine CT to halt Alzheimer’s disease pathogenesis. This study opens new doors for researchers with a wide range of neuropharmacological activities that could be utilized in developing suitable formulations, especially for the treatment of neurodegenerative disorders.