Journal of Applied Pharmaceutical Research (JOAPR)
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Enhancement of flow properties, solubility, and dissolution of the atazanavir by spherical crystallization
Get PDFBackground: The present work aimed to develop spherical agglomerates of Atazanavir (ATZR) with enhanced flow properties, compressibility, solubility, and dissolution. 22 full factorial design approach was employed to develop agglomerates. Methodology: ATZR spherical agglomerates were prepared using bridging solvent Benzene, methanol, HPMC and evaluation for different properties. Then, ATZR immediate release (IR) capsules were formulated using spherical agglomerate, wet granulation, and direct compaction methods. Results and discussion: The spherical agglomerates resulted in a significant enhancement of micromeritic properties. The drug content was ranged from 91.9 % (SAA6) to 97% (SAA2). Drug content and solubility (4.88 to 39.89 mg/ml) were directly related to the concentration of HPMC and inversely related to benzene concentration (p<0.05). Nearly 10.12-fold enhancement in solubility of ATZR was found with spherical agglomerates. FTIR analysis demonstrated excellent compatibility between the drug and the polymer. XRD results indicated the amorphization of pure ATZR during agglomeration. The agglomerates exhibited spherical particle morphology. DSC analysis confirmed the effective encapsulation of the drug. Nearly 100% release was observed within 10 minutes from the F1 capsule formulation containing ATZR spherical agglomerates. Conclusion: The optimized SAA2 spherical agglomerates were utilized to manufacture immediate-release capsules via direct filling (F1). Spherical agglomerates significantly enhanced the flow properties and compressibility of the blend compared to pure ATZR. Drug release from the F1 batch was notably faster than F2 and F3 formulations. The study demonstrates the substantial improvement in flow properties, compressibility, solubility, and dissolution of ATZR using spherical agglomerates
Novel coumarin chalcone derivatives: synthesis, docking, and antimicrobial evaluation
Get PDFBackground: This study synthesized and evaluated a series of coumarin chalcones for their antimicrobial efficacy against microbial and fungal strains. Methodology: Ten new coumarin chalcones were prepared by Claisen- Schmidt condensation by using 4-hydroxy coumarin as a precursor and followed by refluxing obtained intermediate (3-(4-aminophenyl)-3-oxo prop-1-enyl)-4-hydroxy-2H-chromen-one) with substituted aromatic benzaldehyde in the presence of piperidine as a catalyst. IR, 1HNMR, 13CNMR, and GCMS characterized all synthesized compounds. The agar well diffusion method assessed these compounds for antimicrobial activity against various bacterial and fungal strains such as E. coli, P. aeruginosa, B. subtills, S. aureus, and C. albicans. Zone inhibition was measured for each compound (10µL) against all strains. Results and Discussion: The study showed that derivatives 4c, 4e, 4f, and 4g showed strong potential for inhibition towards various fungal and microbial strains. The inhibition zone for 4c and 4e was emerged as 5.48±0.448, 7.02±0.332, 5.62±0.321, 6.81±0.021, 7.72±0.421 and 5.13±0.179, 6.76±0.511, 4.24±0.273, 4.64±0.231, 5.48±0.049 while compound 4f and 4g showed 5.40±0.420, 6.69±0.168, 5.71±0.245, 5.28±0.042, 7.09±0.175, and 4.94±0.814, 6.58±.0160, 6.01±0.455, 6.61±0.021, 6.91±0.414 mm, respectively. Between -7.1 to -10.2Kcal/mol is the range of docking score of derivatives by interactions of DNA gyrase and compounds analyzed. Here, compound 4g exhibited the highest DNA gyrase inhibition, and compound 4c exhibited a strong inhibition with docking scores of -10.2 kcal/mol and -9.8 kcal/mol, respectively. Conclusion: The findings of this work contribute to a better understanding the potential of synthesised compounds as drug candidate against microbial infections through ADMET study
Formulation and in-vitro evaluation of oxaprozin transdermal patches for sustained anti-inflammatory therapy
Get PDFBackground: Inflammation is characterized by pain, altered membrane permeability, increased vascular activity, and protein denaturation. Oxaprozin, a BCS Class II NSAID, is often used to manage inflammation and pain but is limited by poor solubility and extensive first-pass metabolism, which reduces its effectiveness when administered orally. This study aimed to develop and evaluate oxaprozin-loaded transdermal patches as a patient-friendly alternative for sustained anti-inflammatory therapy. Methodology: Transdermal patches were formulated using the solvent-casting technique with hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP K-30) as film-forming polymers, along with plasticizers and permeation enhancers (propylene glycol and DMSO). A Box-Behnken design (13 runs) was employed to optimize the effects of polymer concentrations on adhesion strength and % cumulative drug release. The patches were characterized for thickness, folding endurance, surface pH, moisture content, drug content, and in vitro drug release. Result and Discussion: Pre-formulation studies confirmed drug-excipient compatibility and stability. P1 exhibited optimal performance with a thickness (0.123±0.34 mm), weight variation (94.5±0.56 %), drug content (94.47 %), folding endurance (25±0.1), and in vitro drug release (81.14±6.08 % over 24 hours). The release followed Korsmeyer-Peppas kinetics (R2 = 0.9677), indicating a diffusion-controlled release mechanism. Statistical analysis confirmed significant differences among formulations (p < 0.05) & stability studies showed no changes after 3 months. Conclusion: The optimized oxaprozin transdermal patches, particularly formulation P1, demonstrated uniformity, stability, and controlled drug release, establishing their potential as an effective alternative to oral NSAID therapy. Future in vivo studies are recommended to confirm therapeutic efficacy and clinical applicability
Development and validation of simple HPTLC – UV assay method for determination of quetiapine fumarate concentrations in simulated plasma fluid
Get PDFBackground: Quetiapine fumarate (QTF) is a high-affinity monoaminergic antagonist selective for serotonin Type 2 (5HT2) and dopamine Type 2 (D2) receptors. In this paper, we formulated and validated a simple, reproducible, and convenient procedure for determining QTF concentration in Simulated Plasma Fluid using HPTLC-UV. Methodology: Simulated plasma samples do not require deproteinization. A simulated plasma fluid sample was prepared using a one-step filtration method with a 0.45 µm nylon syringe filter. HPTLC chromatographic separation of test plasma samples was achieved by TLC silica gel aluminium plates 60 F254, which served as the stationary phase. Results and Discussion: The mobile phase consisted of a mixture of methanol and acetonitrile (3:7 v/v), followed by densitometric detection at 296 nm. Well, separated peaks have been noted with retardation factors (Rf) of 0.62. Calibration plots were found to be highly linear (Correlation coefficient r²> 0.99) in the concentration interval of 20–120 ng/mL. Inter and intraday assay precision and accuracy were below 2%. The proposed method avoided the use of a buffer and employed low volumes of simulated plasma samples with plain mobile phase composition. Conclusion: The developed HPTLC–UV assay method was found to be simple, accurate, and reproducible for determining Quetiapine Fumarate in simulated plasma fluid. Validation results confirmed the method's specificity, linearity, precision, and robustness as per ICH guidelines. This method can be effectively applied in routine bioanalytical studies and drug monitoring
Formulation development and characterization of flucinolone acetonide nanoemulsion for ocular drug delivery system
Get PDFBackground: The purpose of this study is to enhance and demonstrate the effectiveness of the corticosteroid drug fluocinolone acetonide in the form of an ophthalmic nanoemulsion. This formulation is designed to improve targeted delivery and ocular penetration, making it suitable for the treatment of conditions such as age-related macular degeneration, diabetic macular edema, and posterior uveitis. Methodology: To formulate the nanoemulsion, we used polysorbate 20 and a castor oil derivative known as HCO-40. The continuous emulsification method was employed to prepare the formulation. Initial batches were tested for key properties, including pH, osmolality, drug content, globule size, and zeta potential. A factorial design approach was applied, in which polysorbate 20 and the castor oil derivative (Cremophor RH 40) were considered independent variables. The nanoemulsion was further evaluated for ocular irritancy using cell line analysis, in vitro scleral permeability, and the Hen’s Egg Chorioallantoic Membrane (HET-CAM) test. Results and Discussion: The optimized batch of the nanoemulsion showed a penetration rate exceeding 80% and a small globule size of 19–20 nm. In vitro tests using human retinal pigment epithelial (ARPE-19) cells and the HET-CAM test indicated that the formulated nanoemulsion is non-toxic and non-irritating to the eye, confirming its cytocompatibility. Conclusion: The developed optimized nanoemulsion formulation of flucinolone acetonide provides improved targeting, non-invasive administration & enhanced patient compliance when used as a topical eye drop for treating ocular diseases such as age-related macular degeneration and posterior uveitis
Design, development, and optimization of mucoadhesive buccal films of ganaxolone for enhanced bioavailability
Get PDFBackground: CDD disorder affects children mainly during their first three months of life. The buccal route offers advantages over oral administration for ganaxolone by avoiding first-pass metabolism and providing direct systemic absorption. This study aimed to formulate and characterise mucoadhesive buccal films of ganaxolone to increase its bioavailability. Methods: Mucoadhesive buccal films were prepared using a solvent casting technique employing HPMC K4M and Moringa gum as polymers. The formulation was optimized using a 32-factorial design, where polymer concentrations were varied systematically to achieve optimal film properties. Nine batches (OF1-OF9) were formulated and evaluated for various physicochemical parameters, mucoadhesive strength, percentage drug content, goat buccal mucosa permeation study, and stability analysis. Results: Based on the findings, the OF8 batch containing optimal polymer ratio (250mg HPMC K4M and 60mg Moringa gum) emerged as the superior formulation with 94.45±0.34% drug content, 15.37±0.58 N/mm² tensile strength, and 7.8±0.57 N mucoadhesive strength. Permeation studies consequently confirmed 96.37% of the drug at 8 hours with a 13.63 µg /cm² /h permeation rate. There was no evidence of drug-excipient interaction in FTIR and DSC analysis. The formulation was set to be stable for 6 months at accelerated conditions (40±2°C, 75±5% RH) with an average tensile strength above 15 N/mm² and an average ex-vivo drug permeation of 93%. Conclusion: This optimized buccal film formulation demonstrates promising potential for clinical application in CDD treatment by offering enhanced bioavailability, controlled release, and patient-friendly administration, which is particularly beneficial for pediatric patients
Harnessing hydrogen-bonding: advancements and applications in pharmaceutical co-crystallization
Get PDFBackground: In the context of supramolecular chemistry, the formation of solid-state structures that exhibit predictable form and function through the use of intermolecular interactions is known as crystal engineering. In crystal engineering, the hydrogen bonds provide a directional and strong interaction between co-formers, helping to create a stable and well-defined crystalline lattice. The formation of hydrogen bonds can modify key properties of a co-crystal, such as solubility, melting point, and mechanical properties, which are valuable in pharmaceutical applications to improve drug efficacy. Fexofenadine co-crystals have been shown to significantly enhance solubility, achieving an 11-fold increase in water and a 2.47-fold increase in hydrochloric acid solutions. Objective: The review primarily focuses on the process of recognizing molecules and forming complex assemblies that are controlled via non-covalent interactions. Methodology: Various strategies, including hydrogen bond-based co-crystal design, are discussed and elaborated upon in this review. Result and Discussion: Reliable tools for developing supramolecular architectures can be obtained by complementarily combining hydrogen bonds with the understanding of robust supramolecular synthons. In addition to bringing different molecules together, these strong supramolecular synthons play a significant role in co-crystallization by adding dimensionality and a degree of directionality to the three-dimensional solid structures. Conclusion: Accurately predicting co-crystal synthesis requires a deep understanding of supramolecular interactions and a carefully selected library of co-formers with functional groups that complement those of the target compound
Formulation development and evaluation of oil-based PLGA nanocarriers of fluticasone propionate
Get PDFBackground: Fluticasone Propionate (FP), a potent corticosteroid, suffers from poor aqueous solubility and limited skin permeability, which reduces its clinical efficacy in topical applications. This work aims to overcome these limitations; oil-based poly(lactic-co-glycolic acid) (PLGA) nanocarriers were developed to enhance the solubility, stability, and sustained release of FP. Methodology: A 3² factorial design was employed to formulate nine batches of PLGA nanocarriers loaded with FP using varying concentrations of PLGA and Capmul MCM. The formulations were evaluated for particle size, zeta potential, drug content, and in vitro drug release. The optimized batch was further characterized using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and X-Ray Diffraction (XRD). Stability studies were conducted over 30 days under accelerated conditions. Results and Discussion: Among all batches, formulation F1 exhibited optimal characteristics, with a particle size of 197.5 nm, a zeta potential of -27.4 mV, and a drug content of 99.85%. The in vitro drug release profile showed a sustained release of 97% over 12 hours. SEM confirmed a spherical morphology with uniform distribution, while DSC and XRD analyses indicated the amorphous dispersion of the drug within the PLGA matrix. The formulation remained physically and chemically stable during the 30-day accelerated stability testing. Conclusion: The study demonstrates that oil-based PLGA nanocarriers effectively enhance the solubility and controlled delivery of Fluticasone Propionate. Although in vivo validation is pending, the system offers promising potential for improving topical corticosteroid therapy in clinical settings. The novelty of this formulation lies in the strategic combination of Isopropyl Myristate and PLGA to create an oil-based nanocarrier platform, which has not been previously reported for Fluticasone Propionate. This approach enables superior drug encapsulation, enhanced skin permeability, and controlled drug delivery
Overcoming chemoresistance in mucinous adenocarcinoma: the impact of tumor microenvironment and genetic alterations
Get PDFBackground: Mucinous adenocarcinoma (MAC) is a rare, aggressive subtype of adenocarcinoma, distinguished by excessive extracellular mucin production. This feature impairs drug penetration and contributes to poor chemotherapy response and chemoresistance. Genetic mutations (e.g., KRAS, BRAF, PI3K/AKT), epithelial-to-mesenchymal transition (EMT), alterations in the tumor microenvironment, and mucin barriers contribute to this resistance. Objective: This narrative review aims to comprehensively summarize the molecular and microenvironmental mechanisms behind chemoresistance in MAC and highlight emerging therapeutic strategies to overcome it. Results: Chemoresistance in MAC arises from oncogenic signaling, immune evasion, hypoxia, and mucin-mediated drug exclusion. Promising approaches include mucolytic agents, small-molecule inhibitors, immune checkpoint inhibitors, RNA-based therapies, and nanoparticle-assisted drug delivery. Precision medicine, which utilizes genomic and transcriptomic profiling, is advancing individualized treatment; however, clinical translation remains limited. Conclusion: Resistance in MAC stems from both genetic and microenvironmental factors. Understanding these mechanisms is crucial for developing more effective, personalized therapies to improve patient outcomes. Future efforts should focus on validating novel therapies through clinical trials, discovering predictive biomarkers, and exploring tumor heterogeneity with multi-omics technologies. Integrating targeted therapies with advanced delivery systems may offer significant advances in treating chemoresistant MAC
Neuroprotective potential of methanolic leaf extracts of Celosia cristata and Callistemon citrinus on scopolamine-induced amnesia in swiss albino mice
Get PDFBackground: The primary reason for memory loss is Alzheimer’s disease, a progressive neurodegenerative condition in specific brain parts. This study aims to illustrate the relative enhancement of memory, along with the neuroprotective and antioxidant properties of methanolic leaf extracts from Celosia cristata and Callistemon citrinus in scopolamine-induced amnesia in mice. Methodology: Methanolic extracts of the leaves of Celosia cristata and Callistemon citrinus were evaluated for their effects on scopolamine-induced impaired learning and memory in Swiss albino mice using behavioral animal models, including the Morris water maze (MWM), elevated plus maze (EPM), and object recognition task (ORT). Antioxidants such as Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Thiobarbituric acid reactive substance (TBARS), and acetylcholinesterase (AChE) were also assessed at different doses, i.e., 200 and 400 mg/Kg of methanolic extracts of Celosia cristata and Callistemon citrinus, as well as their combinations. Results and Discussion: The various doses of Celosia cristata and Callistemon citrinus methanolic leaf extracts significantly modified scopolamine effects in experimental animals. Extracts significantly decreased escape latency (ELT) in the MWM test. Inflexion ratio (IR) in the EPM test was significantly raised by extracts, as well as the discrimination index (DI) in ORT. The SOD and GPx levels were significantly enhanced whereas TBARS significantly reduced by extracts. The significant reduced level of AChE was reported in extract treated mice. The extracts from both plants exhibited significant results at different doses (200 mg/kg and 400 mg/kg) and combination of both plant extracts (MCel+MCal 400) at 400mg/kg dose showed most significant result. Conclusion: The results revealed that methanolic leaf extracts of Celosia cristata and Callistemon citrinus hold potent antiamnesic effects