Journal of Applied Pharmaceutical Research (JOAPR)
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Development and optimization of etrasimod-loaded pH-dependent nanoparticles for colon targeted drug delivery
Get PDFBackground: Etrasimod-loaded pH-sensitive nanoparticles offer a promising strategy for targeted drug delivery to the colon, minimizing systemic exposure and enhancing therapeutic efficacy. A Quality-by-Design framework enables systematic optimization of formulation parameters to ensure robust performance and site-specific release. This represents the first systematic development of pH-responsive nanoparticles for etrasimod delivery and the first application of factorial design optimization for S1P receptor modulator nanoformulations. Methodology: Etrasimod-loaded pH-dependent nanoparticles were prepared via nanoprecipitation using Eudragit S100 and Eudragit RL100 polymers. The formulation was optimised using a 3² full factorial design with polymer concentrations as independent variables. The nanoparticles were characterised by particle size, zeta potential, entrapment efficiency, and drug release. The optimised formulation underwent comprehensive physicochemical characterisation (FTIR, DSC) and 6-month accelerated stability testing. Results and Discussion: The optimised formulation (TF5) containing 90% Eudragit S100 and 10% Eudragit RL100 exhibited optimal characteristics with a particle size of 142.6±5.4 nm, zeta potential of -23.5±1.8 mV, and entrapment efficiency of 73.4±3.2%. FTIR and DSC studies confirmed drug-polymer compatibility with minimal interaction. The in vitro release profile demonstrated controlled initial release (9.8% at 1 hour) followed by complete drug liberation (94.2% at 12 hrs) at pH 7.2. The formulation remained stable for 6 months at 40 °C ± 2 °C and 75% ± 5% RH, with minimal changes in critical quality attributes. Conclusion: The developed pH-dependent nanoparticulate system offers a promising platform for colon-targeted delivery of etrasimod, demonstrating optimal physicochemical properties, controlled release characteristics, and excellent stability. This formulation approach shows potential to improve therapeutic outcomes in inflammatory bowel disease by enhancing colonic drug delivery
Design and optimization of folate-targeted lipid-polymer hybrid nanoparticles co-encapsulating dexamethasone and curcumin for synergistic anti-inflammatory efficacy in rheumatoid arthritis
Get PDFBackground: Rheumatoid Arthritis (RA) is a chronic immune-mediated disorder characterized by synovial inflammation and joint destruction. Current therapies are limited by systemic toxicity and poor bioavailability. This research developed Dexamethasone (Dex) and Curcumin (Cur) loaded Folate Lipid Polymer Hybrid Nanoparticles (DCFLPs) to achieve synergistic anti-inflammatory action for RA. Methodology: DCFLPs were synthesized by the ionic gelation technique. Furthermore, Box-Behnken Design (BBD) formulations were optimized and evaluated for size distribution, PDI, ζ potential, structural features, % encapsulation efficiency (EE), in vitro release profile, and cell line studies using RAW 264.7 cells. Results and Discussion: Optimized DCFLPs revealed an average particle size of 287.8 ± 1.32 nm and PDI 0.25 with positive ζ potential 5.4 mV, and have shown high entrapment efficiencies for Dex (89.12 ± 0.087%) and Cur (98.27± 0.110%). Cytotoxicity assays showed superior anti-inflammatory activity, and enhanced cellular uptake was observed in cell line studies. Conclusion: DCFLPs offer an auspicious approach for targeted RA therapy by combining controlled drug release, reduced systemic toxicity, and enhanced site-specific delivery. These findings suggest that the synthesized formulation has the potential to serve as a viable approach for in vivo translation, future preclinical evaluation, and effective progression towards clinical application in RA management
Therapeutic potential of bioconstituents in the prevention and treatment of rheumatoid arthritis
Get PDFBackground: Rheumatoid arthritis (RA), a joint disease characterized by inflammation and an autoimmune response, affects approximately 1% of the global population. The disruption of immunological tolerance causes the immune system to attack self-molecules, resulting in autoimmune disease. RA is characterized by synovial swelling, accompanied by morning stiffness and joint soreness. Methodology: Herbal pharmacotherapy is now a meaningful focus in the treatment of rheumatoid arthritis. Medicinal plants contain strong active components like flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. Their anti-inflammatory and antioxidant qualities make them a potential treatment option for RA. Results and Discussion: Standard medication aims to prevent further deterioration of the affected joint. This treatment includes several antirheumatic medications, such as methotrexate, biological agents, cytotoxic drugs, immunosuppressants, and NSAIDs. Urinary and respiratory tract infections have been reported in patients treated with certolizumab pegol. Several concerns regarding anti-rheumatoid medication arise during a woman's pregnancy. Therefore, rheumatoid arthritis is now being effectively treated with herbal pharmacotherapy. Conclusion: RA is a chronic autoimmune disorder that primarily affects joints through persistent inflammation. Conventional treatment regimens for RA can lead to the occurrence of adverse effects, such as urinary and respiratory tract infections. Given these challenges, herbal pharmacotherapy is emerging as a safer and more sustainable approach. This review highlights a variety of phytochemicals with anti-inflammatory and antiarthritic properties, including flavonoids, alkaloids, stilbenoids, tannins, and sesquiterpene lactones. It underscores the need for further research to elucidate their mechanisms of action, assess their long-term safety and clinical utility, and compare their efficacy
Chitosan-based in-situ forming polyelectrolyte complexes for ciprofloxacin sustained release tablets
Get PDFBackground: It is not straightforward to create sustained-release (single-unit) oral dosage forms for hydrophilic medicines, which are highly soluble (10 mg/mL) in gastric fluids and have a high dose. This study is an attempt to utilize biopolymer Chitosan-based Polyelectrolyte complex as a retardant to develop and evaluate the sustained release tablet formulations (oral) of Ciprofloxacin hydrochloride. Methodology: Sustained-release tablets were prepared using the traditional wet granulation method, employing a neutralized chitosan solution (1% w/w) at 4°C in 1% acetic acid as the binder. Formulated tablets were assessed for pharmacopoeial and non-pharmacopoeial parameters, as well as in vitro 12-hour drug release studies. The different mathematical models were utilized to examine the pharmacokinetic parameters and elucidate the mechanism of drug release. Results and discussion: The sustained release of the drug for 12 hrs was confirmed through the in vitro release studies. Both formulations, CFX 2 and CFX 3 exhibited 97% and 98% cumulative drug release, respectively, after 12 hr. The dissolution profiles of both formulations were shown to be unaffected by the change in anionic polymers from one to two, as confirmed by dissolution profile comparison studies, with values of similarity factor (f2) 84 and of difference factor (f1) 2. The XRD studies confirmed the in situ formation of a polyelectrolyte complex between chitosan and anionic polymer, as evidenced by the presence of additional peaks in the diffractograms. Conclusion: The polyelectrolyte complexes not only provide a sustained drug release but also prevent the initial burst release of the the drug
Formulation, designing and evaluation of gastro-retentive floating microspheres using silymarin, curcumin and piperine for hepatoprotection
Get PDFBackground: Curcumin, Silymarin, and Piperine are natural phytoconstituents with proven hepatoprotective effects; however, their therapeutic efficacy is limited by poor water solubility and low oral bioavailability. A gastro-retentive floating drug delivery system offers a strategic approach to enhance gastric residence time and improve absorption in the upper gastrointestinal tract. Methodology: Floating microspheres were developed using the solvent evaporation technique with Ethyl Cellulose and Eudragit RS 100 as polymers. A series of trial formulations was statistically optimized using Design Expert® software. The microspheres were evaluated for particle size, buoyancy, entrapment efficiency, drug release profile, and stability. Results and Discussion: The optimized formulation (Batch F3) demonstrated high encapsulation efficiency (>98%) and sustained buoyancy of 95.94% over 8-hour. At the end of 12 hours, cumulative drug release was 66.24% for Curcumin, 68.21% for Silymarin, and 72.82% for Piperine. Drug release followed zero-order kinetics, with the best model fit (R² = 0.9938) observed for Piperine. SEM images confirmed the presence of spherical and uniform microspheres. The formulation remained stable for 90 days under ICH Q1A(R2) conditions. Conclusion: The developed microspheres offer a promising gastroretentive system for controlled delivery of hepatoprotective agents, potentially improving therapeutic outcomes for liver-related disorders
Formulation and evaluation of moxifloxacin-loaded proniosomal gel for ocular delivery
Get PDFBackground: The management of ocular disorders is particularly arduous due to the eye's distinctive anatomy. The cornea serves as a crucial obstacle to medication absorption, restricting the effectiveness of conventional dosage regimens. To address this issue, a proniosomal gel has been developed, comprising a lipid bilayer that emulates the corneal cell membrane, thereby enhancing drug transport across the cornea and resulting in improved bioavailability. Methodology: The Moxifloxacin-loaded Proniosomal gel was developed by the coacervation phase separation method. To determine the physicochemical characteristics of the gel, various evaluation parameters were conducted, including viscosity, pH, FTIR, zeta potential, polydispersity index (PDI), particle size (PS), entrapment efficacy (EE), SEM, and in vitro studies. Results and Discussion: The F5 optimized formulation exhibited a maximum EE of 94.47±0.23%, an ideal pH of 6.8, a PS of 105.4 nm, a PDI of 0.3678, and a zeta potential within ±30 mV. In-vitro drug release and kinetic studies showed that proniosomal gel followed first-order kinetic characteristics of drug released and a biphasic drug release pattern (There is an initial rapid release of the drug, followed by a slower, controlled release over an extended period). Conclusion: Proniosomal gels as drug delivery carriers increased corneal contact, penetration, and retention time in the eye, resulting in sustained action and increased bioavailability
Optimization of fast melting olanzapine tablets using solid dispersion and response surface methodology
Get PDFBackground: Olanzapine is a poorly water-soluble, anti-psychotic drug that belongs to the class of thiobenzodiazepines, which has a bioavailability of 60 – 65%. The purpose of this research work is to enhance the solubility of olanzapine by the solid dispersion technique using different water-soluble carriers, using a phase solubility study using a 24 factorial design, and to incorporate the solid dispersion of olanzapine to formulate fast-melting tablets using different superdisintegrants. Methodology: The fast-melting tablets were prepared using the wet granulation technique and optimized through a 23 full factorial design. The independent variables are sodium starch glycolate (X1), sodium carboxymethyl cellulose (X2), and the method of preparation of the solid dispersion (X3). The dependent variables are hardness (Y1), friability (Y2), disintegration time (Y3), and in vitro drug release studies (Y4). The kinship between independent and dependent variables was demonstrated using contour diagrams. Additionally, the prepared fast-melting tablets were analysed for their weight variation, drug content uniformity, and other dependent variables. Results and Discussion: The fast-melting tablets (batch F6) were considered desirable based on their drug content (99.5% & drug release of 99.3% in 20 minutes, following first–order and Higuchi kinetics. The difference factor f1and f2 similarity factor were found to be 2.43% and 83%, respectively, for the optimized formulation FM2, and the drug release was greater than that of the marketed product. Conclusion: It is evident that the optimized formulation FM2 appears to be a promising system that facilitates the rapid release of olanzapine compared to other formulations
Investigation of thiazolidinedione derivatives for anti-diabetic screening: synthesis, in silico analysis, and in vivo evaluation
Get PDFBackground: Diabetics possess inadequate amounts of insulin to control high glucose levels. Current WHO research estimates that 382 million people have diabetes mellitus, and by 2035, 592 million will. Thiazolidinedione, a physiologically active heterocyclic molecule, including thiazolidine-2,4-dione, is being studied for its anti-diabetic action. Thiazolidinediones, a class of hypoglycaemic drugs used to treat noninsulin-dependent diabetes, were first discovered as insulin-sensitive tissue stimulators. Methodology: In-silico applications like Lipinski's rule of five and Molinspiration evaluate physicochemical characteristics, and Molegro Virtual Docker docks molecules. Additionally, compounds are screened in vivo using alloxan as a diabetes inducer and pioglitazone as a comparator medication. Result and Discussion: Docking results determine the interactions of derivatives with 5U5L's active site (H2, H3, H5, H7, H9, and H14). Compound H3 interacts with Cys285, Tyr327, Ser289, His323, and Ala278, whereas compound H14 involves Ser289, Leu353, Phe360, Cys285, and Tyr473 with the PPAR-γ receptor, yielding docking scores of -128.341 and -129.766, respectively, and an RMSD value of 2.55 Å. Docking results showed anti-diabetic effects for H3 and H14. In animal screening, both compounds demonstrated efficacy against alloxan-induced diabetes models, supporting their computational findings. Conclusion: Pioglitazone interacts with hydrogen bonds involving Ser342, Tyr473, Ser289, Glu291, and Leu228 with a docking score of -118.485, while its co-crystal ligand interacts with Tyr327 and Tyr473 with -121.439. This work demonstrates that the thiazolidinedione pharmacophore is crucial for the discovery of anti-diabetic drugs. Both compounds showed significant anti-diabetic effectiveness in computational and in vivo screening. Thus, more research could prove the compound's anti-diabetic properties
Design, formulation, and evaluation of hydrogel network based microbeads for prolonged release of valacyclovir
Get PDFBackground: This study aimed to formulate and develop hydrogel network-based microbeads for the prolonged release of the antiviral drug Valacyclovir, focusing on the effect of natural gum/polymer ratios in their preparation. Methodology: Microbeads containing Valacyclovir hydrochloride were prepared using the ionotropic gelation method, which involved sodium alginate and gellan gum as the polymers, and aluminum chloride as the crosslinking agent. Result: In the evaluation, the F1 batch exhibited the highest swelling capacity, drug entrapment efficiency, and drug release profile. Across all formulations, the particles were round to oval in shape, with sizes ranging from 598 to 816µm. Drug release kinetics revealed that the Higuchi model best explained the formulations. The surface morphology of the best-performing formulation was examined using scanning electron microscopy (SEM). Discussion: The findings proposed that the prepared microbeads function as swellable matrix-type systems, enabling prolonged drug delivery. The Higuchi model fit supported a diffusion-controlled release mechanism, while the SEM analysis confirmed the suitability of the microbead structure for sustained release applications. Conclusion: These kinds of ionotropically-gelled alginate-based microbeads may improve patient compliance by reducing dosing frequency and enhancing oral bioavailability
Quality by design driven RP-HPLC method optimization for analysis of levothyroxine and liothyronine in bulk and tablet dosage form
Get PDFBackground: Levothyroxine and Liothyronine are widely used in thyroid hormone replacement therapies. Simultaneously quantifying Levothyroxine and Liothyronine is important for managing thyroid hormone deficiency. Aim: This study aims to develop and validate an accurate and robust RP-HPLC method for simultaneously quantifying Levothyroxine and Liothyronine by utilizing Quality by Design (QbD). Methodology: Reversed phase chromatography was performed using a High Performance Liquid Chromatographic System (Agilent Technologies Ltd, 1100 series) equipped with a UV detector. The column used was Agilent C 18 (100 mm x 4.6 mm; 5µm) HPLC Column. The chromatographic separation was carried out using a mobile phase composed of Methanol and Formic acid (0.1%) (50:50 %v/v) with a flow rate of 1.2 ml/min, and a UV detector recorded the response at 254 nm. Design expert was used as software to evaluate experimental design studies (Stat-Ease Inc., Minneapolis, USA, Version 13.0). Result and Discussion: The RP-HPLC method was established to quantify Levothyroxine and Liothyronine simultaneously. The established method was linear, and correlation coefficients (R2) were 0.9993 and 0.9994 for Levothyroxine and Liothyronine, respectively. Retention times of Levothyroxine and Liothyronine were 2.587 minutes and 3.035 minutes. Results of accuracy, precision studies, LOD, and LOQ were found within acceptable limits. Conclusion: A robust RP-HPLC method was developed for the simultaneous quantification of levothyroxine and liothyronine by utilizing a QbD. The QbD technique provided a systematic methodology for identifying and optimizing the critical parameters influencing the method's performance