Quality-by-Design (QbD) has transformed pharmaceutical analytical development by moving from empirical, trial-and-error approaches to systematic, science-based frameworks. This review presents a comprehensive review on the application of QbD principles, also known as Analytical Quality by Design (AQbD), to the development of high-performance liquid chromatography (HPLC) methods. This article is about the basic concepts of AQbD, such as Analytical Target Profile (ATP), Critical Method Attributes (CMAs), Critical Method Parameters (CMPs) and importance of risk assessment and Design of Experiments (DoE) in the development of robust methods. The methodological workflow is described from initial scoping through to the establishment of the Method Operable Design Region (MODR) and the implementation of lifecycle control strategies. Detailed coverage of regulatory views such as the enhanced approach in ICH Q14 and the USP Chapter <1220> lifecycle framework. Recent applications in pharmaceutical dosage forms, bioanalytical and stability indicating methods are reviewed to show the versatility and effectiveness of AQbD. The combination of AQbD and Green Analytical Chemistry (GAC) principles as a new paradigm for sustainable method development is discussed. Emerging trends like integration of artificial intelligence, green analytical chemistry principles and continuous manufacturing paradigms are explored as future directions. AQbD is an indispensable paradigm for modern HPLC method development, providing improved robustness, regulatory flexibility, and analytical efficiency, while guaranteeing consistent product quality and patient safety, the review concludes.
Parkinson's disease is a progressive neurodegenerative disease with motor dysfunction and a broad range of non-motor symptoms. Common neuropsychiatric manifestations, such as anxiety and depression, may interfere with participation in rehabilitation and quality of life overall. Emotional distress before physiotherapy can impair attentional control, reduce motivation, and have detrimental effects on motor learning. This case report describes the possible effects of structured meditation delivered immediately before physiotherapy on neuropsychiatric symptoms and rehabilitation readiness in Parkinson’s disease. A 62-year-old man with a 5-year history of Parkinson's disease (Hoehn and Yahr Stage II) presented with bradykinesia, mild rigidity, gait instability, and prominent anxiety and depressive symptoms that precluded physiotherapy. The patient was on a stable dose of levodopa–carbidopa, and no changes in medication were made during the study period. A structured 25-minute meditation protocol (diaphragmatic breathing, mindfulness-based breath awareness, body scan relaxation, and loving-kindness meditation) was administered immediately before physiotherapy sessions five days a week for six weeks. The Hamilton Anxiety Rating Scale assessed psychological outcomes, the Hamilton Depression Rating Scale, and the emotional wellness domain of the Parkinson’s Disease Questionnaire-39. Anxiety levels were 41.6% lower, depressive symptoms were 44.4% lower, and mental health was 38.7% higher after the intervention. Clinically, we observed improved attentional engagement, emotional stability, and greater persistence during physiotherapy sessions. Structured meditation before physiotherapy may be a useful adjunct intervention to reduce neuropsychiatric symptoms and increase rehabilitation engagement in Parkinson's disease. These initial findings need to be confirmed in larger controlled studies.
Sitagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that has emerged as a mainstay in the treatment of type 2 diabetes mellitus (T2DM) on account of favourable efficacy, safety and tolerability profile. In this comprehensive review, we discuss the therapeutic advantages of sitagliptin, including its glucose-dependent mechanism of action, low risk of hypoglycemia, weight neutrality and proven cardiovascular safety as demonstrated by the landmark TECOS trial. The tablet formulation has been successful in clinical trials but there are large patient populations (paediatric, geriatric, dysphagic and critically ill) that require alternative liquid dosage forms. The formulation challenges of developing a stable sitagliptin oral solution are discussed, in relation to the moisture sensitivity of the drug, pH-dependent stability and the need to optimise palatability. A critical review of recent patent disclosures and formulation studies in the scientific literature shows that judicious selection of buffering agents (pH 4–6), artificial sweeteners (sucralose, acesulfame-K), preservatives (parabens) and thickening agents (hydroxyethylcellulose) are required for the successful development of an oral solution. Moreover, the review summarises the current literature on the development of analytical methods, emphasising the role of reverse-phase high-performance liquid chromatography (RP-HPLC) and the increasing application of Analytical Quality by Design (AQbD) principles for the development of stable and robust assay methods. Formulation science, analytical chemistry and patient-centric design principles can together meet the unmet clinical need for a commercially available, stable and quality-controlled oral solution of sitagliptin.
Acitretin is a first-line retinoid for the management of psoriasis and other hyperkeratotic skin disorders; however, its therapeutic application is limited by poor aqueous solubility, inadequate skin retention, and dose-dependent systemic adverse effects following oral administration. The objective of the present study was to formulate and statistically optimize acitretin loaded nanostructured lipid carriers (NLCs) for improved topical drug delivery and prolonged local drug release. NLCs were synthesized via hot homogenization ultrasonication method and optimized by three factor-three level Box-Behnken experimental design to investigate effect of formulation variables on critical quality attributes like particle size and drug entrapment efficiency. The optimized formulation was well characterised for particle size distribution, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, in vitro drug release and storage stability. The optimized NLCs showed nanosized particles with narrow size distribution, high drug encapsulation efficiency and suitable zeta potential, which suggested good colloidal stability. Scanning electron microscopy confirmed the formation of almost spherical nanoparticles with smooth surfaces and little agglomeration. In vitro release studies indicated a sustained release profile that was mainly controlled by diffusion-controlled kinetics, suggesting an efficient incorporation of the drug into the lipid matrix. Moreover, the optimized formulation showed good stability at the tested conditions and maintained its physicochemical properties during storage. The combined results indicate the potential of statistically optimized nanostructured lipid carriers as a topical delivery system for acitretin by increasing drug encapsulation, improving formulation stability and enabling controlled drug release, thus providing the possibility of improving the therapeutic efficacy while minimizing systemic exposure and related adverse effects in the treatment of chronic inflammatory skin disorders.
Superficial fungal infections represent a significant global health burden, affecting approximately 40 million individuals worldwide, particularly in developing nations. Posaconazole, a potent broad-spectrum triazole antifungal agent, exhibits poor aqueous solubility (0.02 mg/mL) and limited permeability, presenting formulation challenges for topical delivery. The present investigation aimed to formulate and evaluate Posaconazole topical gels using different polymers and study the effect of polymer variation on physicochemical properties, drug release behaviour, and antifungal efficacy. Five gel formulations (F1–F5) were prepared using gelling agents such as Carbopol 934P (1% w/w), Carbopol 940 (1% w/w), HPMC K4M (2% w/w), HPMC K15M (2% w/w) and Poloxamer 407 (20% w/w). Organoleptic characterization, determination of melting point, solubility profile, FTIR spectroscopy, DSC analysis and development of a UV spectrophotometric method were carried out as preformulation studies. The formulations were evaluated for: pH, viscosity, spreadability, extrudability, drug content uniformity, in vitro drug release, release kinetics, antifungal activity and stability. Preformulation studies showed the identity and purity of Posaconazole (melting point 168-172°C) and maximum solubility in DMSO (25.76 ± 0.32 mg/mL). The drug-excipient compatibility was demonstrated by FTIR and DSC. All the formulae showed acceptable physicochemical properties. The formulation F4 (HPMC K15M) showed the best properties: pH 6.72, viscosity 34,760 cP, spreadability 24.38 g·cm/sec, extrudability 95.74% and drug content 99.58%. In-vitro drug release by Higuchi kinetics (R2 = 0.992) was found, with 12 hours cumulative release of 97.84% in F4. The formulation was confirmed to be effective against the antifungal activity of Candida albicans, Aspergillus niger and Trichophyton rubrum. No significant changes were observed in the stability studies carried out under accelerated conditions (40 ± 2°C / 75 ± 5% RH) for three months. The HPMC K15M-based posaconazole gel is a promising topical formulation with desirable physicochemical properties, sustained drug release and excellent stability for effective treatment of superficial fungal infections.
Buccal drug delivery is an attractive alternative to conventional oral dosage forms, which allows the administration of drugs through the vascularised mucosa of the oral cavity, potentially minimising exposure to gastrointestinal degradation and hepatic first-pass metabolism. In the present work, nitroglycerine-loaded buccal oral films were prepared by the solvent casting method and were evaluated for their physicochemical and mechanical properties. The main film-forming polymer used was hydroxypropyl methylcellulose (HPMC) 50 cps, and glycerol was used as a plasticiser. The prepared films were evaluated for appearance, weight variation, thickness, folding endurance, disintegration time and surface pH. The resulting films were homogeneous and transparent. Mean film weights for the formulations F1-F3 ranged from 71.6 to 73.0 mg, and the film thicknesses were from 0.45 to 0.63 mm.
Iron deficiency, chronic inflammation, and decreased endogenous erythropoietin production are the main causes of anemia, a prevalent and crippling consequence of chronic kidney disease (CKD). To raise hemoglobin levels, lower the requirement for blood transfusions, and improve patient quality of life, erythropoietin-stimulating agents (ESAs) are now a mainstay in the treatment of CKD-associated anemia. This study evaluates the efficacy of erythropoietin-stimulating medications in treating anemia in patients with chronic kidney disease. Hemoglobin response, transfusion needs, and clinical improvement were examined as part of a thorough evaluation of CKD patients on ESA therapy. The results show that, when properly dosed and managed, ESA medication dramatically raises and keeps hemoglobin concentrations within therapeutic levels.
The present study aimed to develop and validate a simple, economical, and eco-friendly UV spectrophotometric method for the simultaneous estimation of Esomeprazole (ESO) and Levosulpiride (LEV) in solid dosage forms using hydrotropic solubilization. Sodium benzoate (2 M) was selected as the hydrotropic agent to enhance the aqueous solubility of both drugs and eliminate the need for hazardous organic solvents. UV spectra were recorded in the range of 200–400 nm. The selected analytical wavelengths were 302 nm for Esomeprazole and 278 nm for Levosulpiride. Simultaneous equation and absorbance ratio methods were employed for quantitative analysis. The developed method was validated according to ICH Q2(R1) guidelines for linearity, accuracy, precision, specificity, robustness, LOD, and LOQ. The method demonstrated good linearity, accuracy, and precision with satisfactory recovery values. The proposed method offers a green analytical alternative for routine quality control analysis of Esomeprazole and Levosulpiride in pharmaceutical formulations.
Superficial fungal infections remain a major global health challenge, while the therapeutic performance of topical antifungal agents is often limited by poor skin penetration, inadequate drug retention, and suboptimal bioavailability. Isoconazole nitrate is a potent broad-spectrum imidazole antifungal that exhibits good antimicrobial efficacy but is limited by poor aqueous solubility and low permeation across the stratum corneum. In this study, we describe the Quality-by-Design (QbD)- guided development and optimization of isoconazole-loaded glycerosomes for improved dermal drug delivery. A systematic Quality by Design (QbD) approach was employed including Quality Target Product Profile (QTPP), risk assessment and Box-Behnken experimental design to optimize the phospholipid, cholesterol and glycerol levels to achieve the desired vesicle size, polydispersity index, zeta potential and drug entrapment efficiency. The optimized glycerosomes were prepared by thin-film hydration method followed by probe sonication and loaded into Carbopol-HPMC hydrogel for topical application. The optimized composition showed nanosized and homogenous vesicle distribution with high entrapment efficiency and excellent colloidal stability. Morphological and spectroscopic studies confirmed the spherical shape of vesicles and compatibility of drug with excipients while the hydrogel showed desirable rheological properties, homogeneity, and drug content.
As the global cosmetic industry is moving towards sustainable and bioactive alternatives, the need for goods providing therapeutic advantages without the side effects of synthetic chemicals is increasing. Environmental pollution is a primary factor for skin damage, leading to premature aging, pigmentation and inflammation due to the formation of reactive oxygen species (ROS). The present work focuses on the preparation and assessment of anti-pollution herbal cream using extracts of Green tea (Camellia sinensis) and Moringa (Moringa oleifera) which are rich in antioxidants and anti-inflammatory agents. The cream was formulated as an oil-in-water (O/W) emulsion with suitable excipients to give stability, smoothness and ease of application. The prepared formulation was assessed for morphological and physiological characteristics, pH, stability, spreadability and skin irritation. The formulation showed good physical appearance, homogeneity and stability. Bioactive compounds help to counteract free radicals, reduce oxidative stress, and protect the skin barrier. Overall, the developed cream is a safe and effective herbal formulation for protecting skin against pollution-induced damage.
Obesity is a multifactorial metabolic disorder characterized by abnormal or immoderate fat accumulation that harm health and increases the risk of numerous chronic illnesses such as cardiovascular disorders, Non-alcoholic fatty liver disease, Type 2 Diabetes Mellitus (T2DM), and certain cancers. Despite the availability of pharmacological products for obesity management, their long-term use is often connected with inadequate effect and adverse effects. From The past few years, medicinal plants and culinary spices have attracted significant attention as safer and effective alternatives for obesity control due to their rich content of bioactive phytochemicals such as polyphenols, flavonoids, alkaloids, terpenoids, and saponins. These phytochemicals regulate adipogenesis, lipid metabolism, appetite, thermogenesis, inflammation, insulin signaling, and gut microbiota composition through multiple molecular targets. This chapter provides a comprehensive, original, and critical review of anti-obesity medicinal plants and spices, their active phytochemicals, molecular mechanisms of action, preclinical and clinical evidence, safety considerations, limitations, and future research perspectives.
RA is a chronic autoimmune disease that causes joint inflammation, cartilage deterioration, and systemic oxidative stress. Growing data reveals phytochemicals and bioactive substances have anti-inflammatory and immunomodulatory properties, suggesting supplementary RA treatments. Curcumin, boswellic acids, and quercetin can reduce synovial inflammation and joint damage by inhibiting inflammatory pathways such as NF-κB, TNF-α, IL-1, and IL-6. Anti-inflammatory and antioxidant, these natural chemicals protect cartilage and reduce reactive oxygen species–mediated tissue damage. Synergistic effects of various phytochemical in polyherbal formulations may improve therapeutic efficacy and lower component doses, according to emerging studies. Nanotechnology-based delivery technologies including nanoemulsions and nanoparticles have increased bioavailability and targeted administration of these chemicals, overcoming limitations in conventional herbal extracts. In this review, ethnobotanical knowledge is combined with modern science to evaluate therapeutic plants and extracted phytochemical using HPLC, mass spectrometry, and molecular docking. In RA models, anti-inflammatory markers, oxidative stress indicators, and clinical relevance are key outcomes. The data supports phytochemical as adjuncts or alternatives to RA therapy, emphasizing the need for mechanistic understanding, improved formulations, and new delivery methods to enhance clinical benefits and minimize side effects.
Ocimum gratissimum is widely used in traditional medicine for metabolic disorders; however, systematic evaluation of its metabolic, haematological, and hepatic safety profile remains limited. This study investigated the effects of ethanolic leaf extract of O. gratissimum on glucose homeostasis, haematological indices, oxidative stress markers, liver enzymes, and hepatic histology in rats. Sixteen adult Wistar rats were randomly assigned to four groups (n = 4). The control group received standard feed and water, while treatment groups were administered ethanolic leaf extract of O. gratissimum at doses of 100, 150, and 200 mg/kg body weight daily for 28 days. Blood glucose level was measured, alongside comprehensive haematological profiling. Hepatic oxidative stress markers, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were quantified. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were assessed.
Bilateral tonsilloliths are dystrophic calcifications within tonsillar crypts, incidentally detected on panoramic radiographs, emphasising accurate radiographic interpretation and differentiation from other soft-tissue calcifications.
The objective of this paper is to review the information about the mouth dissolving tablets. Among the different novel drug delivery systems the fast dissolving drug delivery system is rapidly gaining interest in pharmaceutical Industry. Mouth dissolving tablets were developed as an alternative to conventional tablet, capsule and syrups. These dissolve or disintegrate within a minute, without needing water or chewing and enhance the potential for improved compliance in pediatrics and geriatric patients, who have difficulty in swallowing tablets or liquids. In the present review, an account of various formulation considerations, methods of preparations, applications and evaluation parameters of the fast dissolving tablets is compiled.
Abnormal uterine bleeding (AUB) is any menstrual cycle perturbation characterized by alterations in bleeding amount, frequency or duration that occur outside of pregnancy. It makes up to 70% of visits to gynecologists in both outpatient and inpatient practice. Hysteroscopy comes from the Greek words hystero meaning uterus and scopy meaning to look. It is the direct visualization of the cavity of the uterus by a doctor. Before hysteroscopy procedures were performed such as dilatation and curettage (D&C) or pipelle biopsy but it has now been replaced by more accurate and less invasive hysteroscopy. This prospective observational study was conducted from October 2024 to March 2025. A total of 50–80 patients diagnosed with AUB were evaluated using hysteroscopy. The correlation between ultrasonography (USG) findings and hysteroscopic findings was analysed using the Chi-Square test. Most AUB cases occurred in women aged 40–49 years. Significant correlations were found between: Polyps and polypoidal growth (P < 0>).
In this research work, an effort has been made to find the potential synergy of Rubus idaeus for the management of epilepsy through the application of a combination of network pharmacology and molecular docking techniques. The active phytochemicals of Rubus idaeus were searched for with the help of the 'IMPPAT 2.0 and Dr. Duke’s Phytochemical & Ethnobotanical Databases'. Similarly, the 'Comparative Toxicogenomics Database (CTD)' was used for generating the molecular targets of the aforementioned phytochemicals of Rubus idaeus, while the 'GeneCards & MalaCards Databases' were used to obtain the genes responsible for the progression of epilepsy. Using the concept of the 'Venn Diagram Approach,' the common genes among Rubus idaeus and genes for epilepsy were obtained, and they represent the potential target genes for the management of the given disease condition. Finally, the interaction of compounds & targets & disease could be generated with the 'Cytoscape Software & CytoHubba,' while the 'STRING Database' was used to obtain the 'PPI-Network'. And the 'functional enrichment,' 'Gene Ontology,' & 'DisGeNET Pathways Analysis,' respectively, were obtained with the help of the 'Metascape Web Server'. A total of 16 active compounds in Rubus idaeus were discovered, and these targeted 6,744 gene targets. At the same time, a total of 6,251 genes associated with epilepsy were obtained, and their intersection yielded important target genes with the potential of mediating the anti-epileptic properties of Rubus idaeus. These target genes included a major hub gene, estrogen receptor 1 (ESR1), whose importance for the regulation of genes associated with epilepsy was very clear. The molecular docking study also revealed the high binding affinity between alpha carotene and ESR1. In general, a combined analysis of network pharmacology and molecular docking reveals that Rubus idaeus acts on multi-target and multi-pathway to exert anti-epileptic activities, which indicates its potential in the management of epilepsy.
Micro emulsion based Gel formulation provides better application property and stability & makes it dual control release system in comparison to cream and ointment. Topical Micro emulsion based gel drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Many advantages of gels a major limitation is in the delivery of hydrophobic drugs. So to overcome this limitation Micro emulsion based approach is being used so that even a hydrophobic therapeutic moiety can enjoy the unique properties of gels. When gels and Micro emulsions are used in combined form the dosage form are referred as Micro emulsion based gel. It is prepared by mixing an oil-in-water type or waterin- oil type emulsion with a gelling agent. The use of Micro emulsion based gels can be extended in analgesics and antifungal drugs.
This review presents advancement in the field of Micro system Technology and specifically in the area of microneedle-based drug delivery. The objective of this review is to highlight the potential role of microneedles in achieving painless drug delivery of macromolecular drugs across the skin barrier. The dosing in microgram quantities can be done by this type of needle.The stratum corneum is the main barrier for transdermal drug transport. It could be bypassed by microneedles, which have a length of a few tens to a few hundreds of microns. They are usually arranged in arrays and can be used in several ways to enhance transdermal drug transport. Hollow needles of micron dimensions have previously been fabricated and envisioned for use with transdermal patches or infusion pumps to achieve painless delivery of drugs to the skin for local and systemic effects without the need for hypodermic needles. However, little work has been carried out to identify methods to effectively use hollow microneedles for drug delivery. The various method of preparation of microneedles include molding, casting, laser cutting. The in-vivo safety assessment and the evaluation of microneedle have shown that this technique can be used safely.
Lifestyle disorders such as diabetes mellitus, hypertension, obesity and cardiovascular diseases are increasing worldwide due to sedentary lifestyle, unhealthy diet and psychological stress. Ayurveda emphasises preventive healthcare through the principles of Swasthavritta and rejuvenative therapies such as Rasayana. Swasthavritta includes daily regimen, seasonal regimen, dietary discipline and ethical conduct that maintain equilibrium of Doṣha, Dhātu and Mala. Rasayana therapy promotes tissue nourishment, improves metabolic efficiency and enhances Ojas, thereby strengthening Vyādhikṣamatva (immunity). Modern studies have demonstrated immunomodulatory and antioxidant properties of several Rasayana drugs, supporting their role in preventive healthcare. The integration of Rasayana therapy with Swasthavritta practices offers a holistic strategy for enhancing immunity and preventing lifestyle-related disorders.
