Korsemeyer-Peppas Model Research Articles

Development of novel nanoemulsion of pioglitazone used in the treatment of diabetes and its gel form for the treatment of skin diseases

Pioglitazone (PGL), an antidiabetic drug within the thiazolidinedione class, is utilized in managing type-2-diabetes-mellitus. Additionally, it has been observed to exhibit therapeutic effects on various inflammatory markers. PGL falls under BCS Class II, which is defined by its low water solubility and slow dissolution rate. The dual aim of our study was to optimize an oral as well as topical PGL-loaded nanoemulsion (PGL-NE) in order to enhance their bioavailability orally as well as topically. Using the Box–Behnken Design Expert software, Pioglitazone-loaded nanoemulsions (NanoE1 to NanoE17) were optimized. The ultrasonication method was employed following excipients-screening and the preparation of PTPD. The optimized nanoformulation (NanoE13) was determined based on its particle size (137.7 ± 7.92 nm), %Transmittance (91.07 ± 1.03), and PDI (0.221 ± 0.004). NanoE13 exhibited sustained drug release, adhering to the Korsemeyer-Peppas model. When converted into a gel (PGL-NE-Gel), it enhanced permeation of the skin and topical bioavailability. The results of dermatokinetic demonstrated a significant i.e., p˂0.001 increase in CSkinmax & AUC0–8h in skin treated with the optimized PGL-NE-Gel compared to PGL-NE and conventional PGL gel. After 2 weeks, reductions of 40.06 %, 27.34 %, and 37.45 % were observed for diabetic control, PGL-S, and PGL-NE, respectively. PGL-NE also significantly lowered the levels of blood-glucose i.e., p < 0.05 as compared to the diabetic-control -group throughout the experiment. We successfully developed a novel PGL-NE and PGL-NE-Gel, which enhanced the solubility, skin permeation, and bioavailability of Pioglitazone for both oral and topical applications.

Modeling and comparison of dissolution profiles for different brands of albendazole boluses

BackgroundAddressing critical veterinary drugs, especially drugs with solubility problems like albendazole, and their implications for therapeutic efficacy, in-vitro dissolution studies can indeed provide valuable insights into how different brands of albendazole boluses perform under standardized conditions, helping to assess their dissolution profiles and potential bioavailability.MethodsSix brands of albendazole 300 mg boluses were collected from December 2020 to May 2021 G.C. The laboratory work was conducted from December 2020 to May 2021 in the National Animal Products and Veterinary Drugs and Feed Quality Assessment Centre (APVD-FQAC) laboratories. The collected brands from government veterinary clinics and private veterinary shops were subjected to model independent and dependent parameters. The dissolution test was conducted according to the USP monograph.ResultsThe study found that none of the six brands met the requirements of the dissolution test, as their API release was less than 80% within the specified 60-minute timeframe according to USP standards. Model independence indicated that only one brand (Alb002 = 3.72) achieved a difference factor of ≤ 15%. The remaining four brands (4/6) did not meet this criterion. However, the similarity factor (f2) revealed that all five brands (5/6) were comparable to the comparator products, with f2 values of \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:$$\\end{document}50%. The mean dissolution time results confirmed that three brands (3/6) had the highest dissolution rate and the fastest onset of action. The model-dependent kinetics indicated that the Weibull and Korsemeyer-Peppas models were the best fit for the release of drug substances.ConclusionThe study highlights issues with albendazole boluses’ quality, highlighting the need for national in-vitro dissolution studies. These recommendations could improve quality control, streamline regulatory frameworks, and offer practical, cost-effective methods for evaluating drug efficacy and safety, ensuring veterinary pharmaceuticals meet safety and efficacy standards.

Design of quetiapine fumarate loaded polyethylene glycol decorated graphene oxide nanosheets: Invitro-exvivo characterization

Quetiapine Fumarate (QF) is an atypical antipsychotic with poor oral bioavailability (9%) due to its low permeability and pH-dependent solubility. Therefore, this study aims to design QF-loaded polyethylene glycol (PEG) functionalized graphene oxide nanosheets (GON) for nasal delivery of QF. In brief, GO was synthesized using a modified Hummers process, followed by ultra-sonication to produce GON. Subsequently, PEG-functionalized GON was prepared using carbodiimide chemistry (PEG-GON). QF was then decorated onto the cage of PEG-GON using the π-π stacking phenomenon (QF@PEG-GON). The QF@PEG-GON nanocomposite underwent several spectral characterizations, in vitro drug release, mucoadhesion study, ex vivo diffusion study, etc. The surface morphology of QF@PEG-GON nanocomposite validates the cracked nature of the nanocomposite, whereas the diffractograms and thermogram of nanocomposite confirm the conversion of QF into an amorphous form with uniform distribution in PEG-GON. Moreover, an ex vivo study of PEG-GON demonstrates superior mucoadhesion capacity due to its surface functional groups and hydrophilicity. The percent drug loading content and percent entrapment efficiency of the nanocomposite were found to be 9.2±0.62% and 92.3±1.02%, respectively. The developed nanocomposite exhibited 43.82±1.65% drug release within 24h, with the Korsemeyer-Peppas model providing the best-fit release kinetics (R2: 0.8614). Here, the interlayer spacing of PEG-GON prevented prompt diffusion of the buffer, leading to a delayed release pattern. In conclusion, the anticipated QF@PEG-GON nanocomposite shows promise as a nanocarrier platform for nasal delivery of QF.

Improved mucoadhesivity of polyelectrolyte complexes films by electrospinning for the release of nystatin in the oral cavity

This work aimed to obtain and characterize chitosan-gum arabic polyelectrolyte complex films loaded with nystatin employing the “Solvent-Casting” technique. These films were covered with electrospun nanofibers of polycaprolactone-polycarbophil (Noveon® AA-1) to improve the mucoadhesivity of the system with the objective of increasing the residence time in the oral zone and act as sustained release systems of the drug. The topography of the films was determined by SEM, while the interaction of the polymers was evaluated by FTIR, DSC and TGA. The antimicrobial activity of the film was tested against a strain of Candida species, and the mucoadhesión capacity was determined in an in vitro model. The films are mucoadhesive and generate sustained release that can be explained by the Korsemeyer-Peppas model. Furthermore, significant antimicrobial activity was found. The films and their components showed a non-toxic to slight cytotoxic activity. These results indicate that these films based on polyelectrolyte complexes, potentiated by electrospun fibers are a plausible system for the controlled release of nystatin in the oral cavity.

Modulation of Biophysical Cues in Nature Inspired Patterning of Porous Silk Fibroin Scaffold for Replenishable Controlled Drug Delivery.

In our daily lives, cuts and wounds are unavoidable. while they are generally minor, sometimes they do turn serious. While a sticking plaster might be enough in most cases, critical situations like surgical wounds, lacerations, gunshot wounds, accidental skin injuries, diabetic wounds, and other cutaneous deep cuts may require implants and simultaneous medications for healing. From the biophysical standpoint one of the least explored aspects to surmount these hurdles is the internal force-based physical surface stimulus crucial for cellular sensing at the time of wound repair. With more people needing medical attention for wound healing, smart patches will be an integral part of the future generation of wound treatment. We report fabrication of a novel biomimetically patterned silk fibroin porous scaffold with an approach to ampicillin loading and replenishment by joining a polytetrafluoroethylene (PTFE) catheter attached 18G butterfly intravenous infusion needle at the bottom of the substrates. In vitro swelling study reveals that the patterned substrates show less swelling compared to that of the other variants and consequently less in vitro degradation. The ampicillin release patterns from the scaffolds follows the Korsemeyer-Peppas model depicting surface hydrophobicity mediated non-fickian first-order anomalous controlled release. The scaffolds show remarkable antibacterial efficacy against Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli. Four distinct cell-matrix adhesion regimes were investigated for the fibroblasts to eventually form cell sheets all over the hierarchical surface structures. The fluorescence images after DAPI and FDA staining clearly demonstrates that the patterned surface to be superior to its other variants. A comparative study among molecular expressions of collagen I, vinculin, and vimentin using immunofluorescence, substantiated the patterned surface to be superior to others. The work report potential development of a deep cutaneous wound healing drug replenishable implant with biophysical cues capable of controlling fibroblast behavior and release kinetics of ampicillin. This article is protected by copyright. All rights reserved.

Antibacterial and anticancer activity of poly (ɛ-caprolactone)/doxorubicin/Costus arabicus L. root smoke composite nanofibers against lung cancer

The combination of plant-derived agents with chemotherapy drugs could enhance the cytotoxicity of drugs in cancer cells and could improve the biocompatibility of drugs in normal cells. In the present study, the dichloromethane fraction of Costus arabicus L. root smoke (CALRS) and doxorubicin (DOX) have been simultaneously incorporated into the poly (ɛ-caprolactone) (PCL) nanofibers. The synthesized nanofibrous samples were characterized using Fourier-transform infrared spectroscopy, gas chromatography–mass spectrometry, and scanning electron microscopy analysis. The antibacterial, antiparasitic, and anticancer activities of synthesized nanofibers were investigated. The pharmacokinetic models such as Korsmeyer-Peppas, Higuchi, and zero-order were applied to analyze the DOX release mechanism from nanofibers. The continuous release of DOX from PCL/CALRS 5%/DOX 10% nanofibers was occurred during 7 days and the Korsemeyer-Peppas model could describe the DOX release data. The results indicated that the DOX and CALRS dual agents-loaded nanofibers indicated the highest antibacterial activity on both gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria and highest anticancer activity on A549 lung cancer cells death compared to pure DOX, CALRS, and DOX loaded-PCL nanofibers.

Quality evaluation of the Azithromycin tablets commonly marketed in Adama, and Modjo towns, Oromia Regional State, Ethiopia.

Azithromycin is a therapeutically" relevant macrolide antibiotic registered on the Essential Medicines List of the World Health Organization. The fact that medicine is selected as an essential drug doesn't mean that it is of good quality. Hence, a continuous quality evaluation of the drug should be mandated to verify that the right medication is available on the market. To evaluate the quality of Azithromycin Tablets commonly marketed in Adama, and Modjo town, Oromia Regional State, Ethiopia. All six brands were subjected to in-vitro quality control tests, which were carried out according to procedures described in the manufacturer's method, the United States Pharmacopeia, and the WHO inspection tool. All quality control parameters were compared by one-way ANOVA. Statistically, significant difference was considered when P<0.05. The in-vitro dissolution profiles of the brands were also compared statistically using the post-hoc Dunnett test, model-independent and model-dependent approaches. All of the evaluated brands agreed with WHO visual inspection criteria. All of the tablets achieved the thickness, and diameter test requirements of the manufacturer's specification (±5%). All brands passed the hardness, friability, weight variation, disintegration, identity, and assay tests as stipulated by USP. The dissolution rate was more than 80% in 30 minutes, which was within the USP specification. The model-independent parameters have confirmed that only two brands (2/6) were deemed better brands for interchangeability. Weibull and Korsemeyer's Peppas model were the best release models. All of the evaluated brands passed the quality specification. The model dependent approaches revealed that drug release data fit well to the Weibull, and Korsemeyer's Peppas release models. However, the model-independent parameters have confirmed that only two brands were deemed better brands (2/6) for interchangeability. Due to the dynamic nature of low-quality medications, the Ethiopian Food, and Drug Authority should keep an eye on marketed products to guarantee their quality, especially for drugs like azithromycin for which non-bioequivalence data from the study has revealed a clinical concern.

Development and in-vitro evaluation of chitosan and glyceryl monostearate based matrix lipid polymer hybrid nanoparticles (LPHNPs) for oral delivery of itraconazole

Itraconazole (ICZ) is a broad spectrum antifungal drug, but used as second or third line therapy due to its low and erratic oral bioavailability. This work was carried out to prepare and characterize matrix type lipid-polymer hybrid nanoparticles (LPHNPs) for dissolution enhancement of ICZ. LPHNPs were prepared using solvent diffusion/emulsification technique. Matrix LPHNPs were composed of chitosan (polymer), glyceryl monostearate (lipid) and poloxamer 188 (stabilizer). LPHNPs loaded with ICZ (LPHNPs-1, LPHNPs-2, LPHNPs-3 and LPHNPs-4) were developed using varying concentration of chitosan whereas LPHNPs (LPHNPs-5, LPHNPs-6, LPHNPs-7 and LPHNPs-8) were prepared using varying concentrations of poloxamer 188. LPHNPs loaded with ICZ were further evaluated for entrapment efficiency, particle size, polydispersity index (PDI), zeta potential and dissolution profiles at biorelevant pH conditions. The particle size (LPHNPs-1 to LPHNPs-4) was found to be in range of 421–588 nm with PDI values 0.34–0.41. The particles size of LPHNPs-5 to LPHNPs-8 was found to be in range of 489–725 nm with PDI 0.34–0.74. The entrapment efficiency of LPHNPs-1 to LPHNPs-4 was found to be in range of 85.21%–91.34%. The entrapment efficiency of LPHNPs-5 to LPHNPs-8 was found to be in range 78.32%–90.44%. . The scanning electron microscopy of optimized formulations LPHNPs-1 and LPHNPs-5 indicated formation of oval shaped nanoparticles. DSC thermogram of ICZ loaded LPHNPs also depicted the conversion of crystalline form of ICZ into amorphous form demonstrating the internalization and dissolution enhancement of drug in the hybrid matrix. The cumulative drug dissolved at acidic pH 1.2 was found to be 23.3% and 19.8% for LPHNPs-1 and LPHNPs-5 respectively. Similarly at basic pH values 7.4, cumulative amount of drug dissolved was 90.2% and 83.4% for LPHNPs-1 and LPHNPs-5 respectively. Drug dissolution kinetics exhibited fickian diffusion best described by Korse-meyer Peppas model. The results suggested that chitosan and glyceryl monostearate based matrix LPHNPs could be used as promising approach for dissolution enhancement of ICZ which could further increase its bioavailability.

An Alternating Magnetic Field-Controlled Drug Delivery System Based on 4,4′-Azobis (4-cyanovaleric Acid)-Functioned Fe3O4@Chitosan Nanoparticles

Herein, we designed chitosan-coated Fe3O4 nanocomposites for the control release of drugs by an alternating magnetic field (AMF). The chitosan-coated Fe3O4 nanoparticles (Fe3O4@CS) were prepared by a alkaline co-precipitation method, and then, the model drug toluidine blue (TB) was covalently grafted onto the surface of the nanocomposite by a two-step amide reaction with the thermosensitive molecule 4,4'-azobis (4-cyanovaleric acid) (ACVA) as the linker group. The prepared nanocomposites were superparamagnetic and showed high magnetization saturation (about 54.0 emu g-1). In vitro hydrothermal release studies showed that most parts of the TB would be effectively enclosed within the nanocarriers at lower ambient temperatures (23 or 37 °C) due to the molecular bonding of ACVA. The results of kinetic fitting of hydrothermal release data showed that TB released from nanoparticles followed first-order kinetics (R2 > 0.99) and the Korsemeyer-Peppas model (R2 > 0.99, n < 0.5). Most importantly, a single magnetron release experiment demonstrated an approximately linear relationship between the cumulative release of the drug and the duration of action of AMF (R2 = 0.9712). Moreover, the increase in the cumulative release of the drug can be controlled by controlling the switch of the AMF generation device. Therefore, the ACVA-modified Fe3O4@CS nanocarrier designed in this study is a promising model for drug delivery that enables the control of drug release dose by AMF.

Novel Black Seed Polysaccharide Extract-g-Poly (Acrylate) pH-Responsive Hydrogel Nanocomposites for Safe Oral Insulin Delivery: Development, In Vitro, In Vivo and Toxicological Evaluation.

Oral delivery of insulin has always been a challenging task due to harsh gut environment involving variable pH and peptidase actions. Currently, no Food and Drug Administration (FDA) approved oral insulin formulation is commercially available, only intravenous (IV) or subcutaneous (SC) routes. Therefore, it is really cumbersome for diabetic patients to go through invasive approaches for insulin delivery on daily basis. In the present study, a novel pH-responsive hydrogel nanocomposite (NC) system was developed and optimized for safe oral delivery of insulin. Black seed polysaccharide extract-based hydrogel (BA hydrogel) was formulated by free radical polymerization and loaded with insulin. Blank BA hydrogel was also incorporated with insulin-loaded montmorillonite nanoclay (Ins-Mmt) to form an Ins-Mmt-BA hydrogel NC and compared with the insulin-loaded hydrogel. Swelling, sol-gel analysis and in vitro release studies proved that Ins-Mmt-BA6 hydrogel NC has the best formulation, with 96.17% maximum insulin released in 24 h. Kinetic modeling applied on insulin release data showed the Korsemeyer-Peppas model (R2 = 0.9637) as the best fit model with a super case II transport mechanism for insulin transport (n &gt; 0.89). Energy Dispersive X-ray (EDX) Spectroscopy, Fourier Transformed Infrared (FTIR) spectroscopy and Powdered X-ray diffraction (PXRD) analysis results also confirmed successful development of a hydrogel NC with no significant denaturation of insulin. Toxicity results confirmed the safety profile and biocompatibility of the developed NC. In vivo studies showed a maximum decrease in blood glucose levels of 52.61% and percentage relative bioavailability (% RBA) of 26.3% for an Ins-Mmt-BA hydrogel NC as compared to BA hydrogels and insulin administered through the SC route.

Formulation Development and In Vitro/In Vivo Characterization of Methotrexate-Loaded Nanoemulsion Gel Formulations for Enhanced Topical Delivery

Methotrexate-loaded oil-in-water nanoemulsion formulations were prepared using the high shear homogenization technique. A drug excipient study (ATR-FTIR) was carried out to investigate the compatibility between the drug, the polymers, and its admixtures. The thermal stability of the nanoemulsion formulations was evaluated by subjecting them to a heating and cooling cycle. The prepared nanoemulsion formulations (FNE1 to FNE6) were evaluated for particle size, PDI value, and entrapment efficiency (EE). They were analyzed for morphological information using transmission electron microscopy. The drug (methotrexate)-loaded nanoemulsion formulations (FNE2, FNE4, and FNE6) were then converted into nanoemulsion gel formulations by adding 1% chitosan (polymer) as a gelling agent. The nanoemulsion gel formulations (FNEG2, FNEG4, and FNEG6) were investigated for physicochemical parameters, viscosity, spreadability, extrudability, drug content, and skin irritation. Various penetration enhancers (olive oil, clove, and almond oil) were employed to examine the potency of the prepared nanoemulsion gel formulations. In vitro drug release, ex vivo permeation, skin drug retention, and stability tests were carried out for evaluation of the prepared nanoemulsion gel formulations (FNEG2, FNEG4, and FNEG6). The data obtained from the in vitro study were subjected to the kinetic model, and the Korsemeyer-Peppas model was best fitted to the data. The nanoemulsion gel formulation FNEG6 showed the maximum controlled drug release and followed an anomalous, non-Fickian release mechanism. The use of almond oil in the preparation of the nanoemulsion gel formulation FNEG6 helped the penetration of the drug across stratum corneum and the restructuring of the properties of skin and resulted in a higher penetration and retention of methotrexate in a deeper layer of the skin. The current study concluded that the methotrexate-loaded nanoemulsion gel formulation FNEG6 showed the best optimum release, permeation, and retention results as compared to the available oral tablets' formulations, followed by a low serum concentration and the maximum drug retention, which is beneficial in treating skin infections and reducing systemic toxicity.

Docetaxel-loaded borage seed oil nanoemulsion with improved antitumor activity for solid tumor treatment: Formulation development, in vitro, in silico and in vivo evaluation

In the present work, docetaxel-nanoemulsion (DTX-NE) was developed with the aim to improve its therapeutic activity while reducing the side-effects by targeted delivery approach. The unique approach about the developed formulation was use of borage seed oil as the oil phase which has abundant gamma-linolenic acid (GLA) in it and has been previously reported for its anticancer activity. DTX was solubilized in Borage oil and the system was emulsified using Phospholipid (Lipoid E−80). The nanoemulsion was developed by high shear homogenization and ultrasonication. Systematic optimization of critical factors was carried out using Box-Behnken design. The optimized nanoemulsion showed particle size (180.2 ± 4.5 nm), zeta potential (−33.7 ± 1.9 mV) and PDI (0.178 ± 0.01) within the desired limits. The drug entrapment efficiency was found to be 96.41 ± 4.7% while drug loading was found to be 12.87 ± 1.3%. Further, FTIR, DSC and XRD analysis revealed compatibility of the drug with the excipients in addition to complete drug solubilization and entrapment. Further, in vitro release study performed in PBS (pH 7.4) indicated a biphasic profile while release kinetic evaluation showed best fitting as per Korsemeyer-Peppas model with drug release through Fickian diffusion mechanism. In silico docking performed of DTX and GLA suggested excellent binding with microtubule subunit with the binding affinity of −6.4 kcal/mol and −5.7 kcal/mol, respectively. In vivo pharmacokinetic studies in Albino Wistar rats indicated significant improvement in AUC (3.9-folds), t1/2 (2.0-folds) and MRT (4.0-folds) from DTX-NE vis-à-vis the plain drug, respectively. Furthermore, antitumor efficacy of DTX-NE showed significant reduction in the tumor growth (3.17-times) than the free drug and marketed formulation (Taxotere®).

Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery of ciprofloxacin

Many formulation strategies have been employed to improve ocular bioavailability of topical eye drops. The aim of this study was to develop and evaluate a series of solid lipid nanoparticles coated with poly(2-ethyl-2-oxazoline) and chitosan for ocular delivery of ciprofloxacin. Ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) (PSLN) formulation was prepared by a combination of melt-emulsion sonication and low-temperature solidification methods. A Box-Behnken design, was employed to statistically optimize the effects of the amount of drug (X1), lipid:polymer ratio (X2) and surfactant concentration (X3) on particle size (Y1) and entrapment efficiency (Y2). Analysis of variance was used to validate the optimization design; and regression equations and response surface plots were generated. The optimized formulation was selected through numerical point prediction approach. These nanoparticles were characterized using dynamic light scattering, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). In vitro drug release and corneal permeation studies were carried out, while the mucoadhesive properties were evaluated ex vivo using porcine corneal tissue. The particle size and zeta potential of the optimized formulations ranged from 141 to 213 nm and +24.6 to −35.6 mV, respectively. PSLN possessed higher encapsulation efficiency than chitosan-coated solid lipid nanoparticles (CSLN). The in vitro drug release from all the formulations showed an initial burst release followed by prolonged release over 24 h. The release mechanism followed Korsemeyer-Peppas model and Fickian diffusion (n < 0.5). DSC revealed lower enthalpy and crystallinity of the formulations as also detected by PXRD, while TEM showed spherical particles in the lower nanometer range with a layer of polymer coating. The results of this study demonstrated that CSLN exhibited higher mucoadhesion and retention on corneal tissues compared with PSLN and also showed higher flux and apparent permeability, but with lower entrapment efficiency.

Investigating the use of Liquisolid Compact Technique for Pioglitazone HCl

The aim of present study is to enhance the dissolution of poorly water soluble drug of Pioglitazone HCl by liquisolid compact technique. Liquisolid compact were prepared using propylene glycol as non-volatile solvent, Avicel PH102 as carrier and Aerosil 200 as coating material, sodium starch glycolate as superdisintegrant.The compatibility of excipients and drug was confirmed by FT-IR studies. The dissolution studies for prepared liquisolid tablet were distinctly higher as compared to directly compressed tablets which show significance increased in wetting properties and surface area of drug available for dissolution. The optimized PIO-7 liquisolid formulation shows acceptable flow properties, faster disintegration time and superior dissolution profile. The optimized formulation of liquisolid pioglitazone tablet shows higher drug release when compared to marketed formulation. The mechanism of drug release studied for best formulations where fitted in accordance with higuchi model and korsemeyer peppas model it is evident that a linear relationship was obtained showing that is an apparent first order process.

Solubility Enhancement of Poorly Water Soluble Drug by Using β Cyclodextrin

Aceclofenac complex is prepared by kneading method of inclusion complexation. The aim of present work is to improve the solubility and dissolution properties of a poorly water soluble drug aceclofenac, by inclusion complexation technique. Two components namely β cyclodextrin and span 60 were used in this study, β CD is used as complexing agent and span 60 as surfactant which helps in increasing solubility and dissolution. The prepared Aceclofenac complex is evaluated in terms of compatibility, solubility, dissolution behavior with the help of FTIR, DSC, In vitro dissolution studies. The complexation parameter of β CD had an impact on the solubility of drug. The solubility of complexes was progressively improved when compared to pure Aceclofenac drug in water. The prepared Aceclofenac complexes were subjected to dissolution study. At the end of 60 min of dissolution study 22.32±0.42 of pure drug was dissolved. The prepared complexes showed 85.35±0.71 at 60 min. The percent of drug dissolved increased for the complexes prepared with high concentration of β CD. The study showed that complexing property of β CD and surfactant action of span 60 has its influence on both solubility and dissolution of the prepared inclusion complexes. MDT and % DE was evaluated for the all the prepared complexes. Aceclofenac complexes prepared with high concentration of β CD showed lower MDT and higher % DE compared to pure Aceclofenac. The pure and complexed Aceclofenac were characterized by DSC studies. DSC studies showed that there was no appreciable change in the melting endotherm of prepared complexes compared to that of pure drug. The drug release from the above follows Korsemeyer-Peppas model and release mechanism was Non- Fickinian.&#x0D; Keywords: Aceclofenac, inclusion complex, kneading method, complexing agent, solubility, dissolution.

Design and evaluation of hyaluronic acid coated plga nanoparticles of raloxifene hydrochloride for treatment of breast cancer

Context In the present study, Hyaluronic acid coated Raloxifene loaded PLGA nanoparticles have been developed to improve the anticancer potential and reduce side effects associated with the drug. Aim and Objectives The investigation was aimed to formulate and optimize Raloxifene hydrochloride loaded PLGA nanoparticles with surface modification using hyaluronic acid as a targeting moiety. To perform physicochemical characterization, in vitro cytotoxicity study (using MCF-7), in vitro drug release study and in vivo pharmacodynamic study of optimized formulation. Methodology Raloxifene hydrochloride (RALH) loaded PLGA nanoparticles were prepared by nanoprecipitation technique, followed by surface modification with hyaluronic acid. Formulation was optimized by using 23 factorial design and characterized by physicochemical, in vitro drug release, in vitro cytotoxicity studies and in vivo pharmacokinetics. Results and discussion The particle size, PDI, zeta potential, entrapment efficiency and loading capacity of spherically shaped RALH loaded nanoparticles was 207.3 ± 4.2 d.nm, 0.218 ± 0.127, -28.3 mV, 43.75 ± 1.2% and 7.55 ± 1.14% respectively. The in-vitro drug release showed sustained release and followed Korsemeyer-Peppas model with non fickian release pattern. The in-vitro cytotoxicity study of drug loaded NPs by MTT assay on MCF-7 breast carcinoma cell showed anti-cancer activity after 48 hrs of treatment. Conclusion The results of the present investigation suggested that RALH loaded HA modified PLGA nanoparticles showed sustained drug release with anticancer activity and can be promising approach for treatment of breast cancer.

Formulation and Characterization of Modified Release Microspheres of Lornoxicam Using Okra Gum as Natural Polymer and Ethyl Cellulose as Synthetic Polymer

Objective: The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications in the world because of their demonstrated efficacy in reducing pain and inflammation. The arthritis, pain and inflammation are effectively treated with Lornoxicam, an effective NSAIDs. Because the drug is weakly acidic, it is absorbed easily in the GI tract, and has a short biological half-life of 3 to 5 hours. To meet the objectives of this investigation, we developed a modified release dosage form to provide the delivery of lornoxicam at sustained rate which was designed to prolong its efficacy, reduce dosage frequency, and enhance patient compliance. The present research work was focused on the development of lornoxicam microspheres using natural polymer like okra gum extracted from the pods of Abelmoschus esculentus Linn. and synthetic polymer like ethyl cellulose along with sodium alginate prepared by Ca2+ induced ionic-gelation cross-linking in a complete aqueous environment were successfully formulated.&#x0D; Materials and Method: The microspheres were prepared by using sodium alginate with natural polymer (okra gum) and synthetic polymer (ethyl cellulose) in different ratios by Ca2+ induced ionic-gelation cross-linking. The formulations were optimized on the basis of drug release up to 12 hrs. The physicochemical characteristics of Lornoxicam microspheres such as drug polymer interaction study by Fourier Transform Infrared (FTIR) and further confirmation by Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). The formulated microspheres were characterized for particle size, percentage drug entrapment efficiency, micromeritic properties, surface morphology, percentage swelling index, in-vitro drug release study and mechanism of drug release.&#x0D; Results and Discussion: The FTIR Spectra revealed that there was no interaction between polymer and Lornoxicam which was further confirmed by DSC and XRD. All the formulated Lornoxicam microspheres were spherical in shape confirmed by SEM. The microspheres exhibited good flow properties and also showed high percentage drug entrapment efficiency. All the batches have excellent flow properties with angle of repose in the range of 25.38° ± 0.04 to 30.41° ± 0.07, carr’s index and hausner’s ratios in the range of 10.40% ± 0.018 to 16.66% ± 0.012 and 1.128 ± 0.09 to 2.225 ± 0.01, respectively. The optical microscopic studies revealed that the mean particle size of all the formulations were found in the range of 819.46 ± 0.07 to 959.88 ± 0.02 μm and percentage of drug entrapment were found to be between 72.35 ± 0.02 to 90.00 ± 0.05. Swelling index of prepared microspheres revealed that with increasing the polymer ratios, there were increase in the swelling of prepared microspheres, showing in the range of 600.76 ± 0.42 to 690.11 ± 0.03% for okra gum microspheres at the end of 9 hr in comparison with ethyl cellulose microspheres which ranges between 179.71 ± 0.07 to 227.73 ± 0.05% at the end of 7 hr. In-vitro drug release of prepared microspheres formulation code LSO4 and LSE4 were found to be 88.654 ± 0.25% and 93.971 ± 0.20% respectively at the end of 12 hr. It was suggested that increase in polymer concentration, the drug release from the prepared microspheres got retarded producing sustained release of lornoxicam. In-vitro drug release data obtained were fitted to various release kinetic models to access the suitable mechanism of drug release. Drug release from lornoxicam-loaded alginate-okra gum microspheres followed a pattern that resembled sustained release (Korsemeyer-Peppas model) (R2 = 0.9925 to 0.9951), and n ≤ 1 indicated anomalous diffusion (non-Fickian), supercase-II transport mechanism LSO4 (n = 1.039) over a period of 12 hour underlying in-vitro drug release. Moreover, zero order model (R2 = 0.9720 to 0.9949) were found closer to the best-fit Korsemeyer - Peppas model.&#x0D; In addition, the drug release from lornoxicam-loaded alginate-ethyl cellulose microspheres also follow Korsemeyer-Peppas model (R2 = 0.9741 to 0.9973) with near to Hixson-Crowell model (R2 = 0.9953 to 0.9985) and n &lt; 1 indicated non-Fickian diffusion or anomalous transport mechanism. Moreover, first order model with non-Fickian diffusion mechanism (R2 = 0.9788 to 0.9918) were found closer to the best-fit Korsemeyer-Peppas model/ Hixson-Crowell model.&#x0D; Conclusion: The present study conclusively demonstrates the feasibility of effectively encapsulating Lornoxicam into natural polymer (okra gum) and synthetic polymer (ethyl cellulose) to form potential sustained drug delivery system. In conclusion, drug release over a period of 12 hrs, could be achieved from these prepared microspheres. A pH-dependent swelling and degradation of the optimized microspheres were also observed, which indicates that these microspheres could potentially be used for intestinal drug delivery.

Design expert as a statistical tool for optimization of 5-ASA-loaded biopolymer-based nanoparticles using Box Behnken factorial design

BackgroundThe overall objective was to prepare a highly accurate nanocarrier system of mesalamine for the treatment of ulcerative colitis with increased therapeutic efficacy and targeting. In the formulation of nanocarrier systems, optimization is a critical process for understanding nanoformulation variables and quality aspects. The goal of the present work was to determine the effect of independent variables, i.e., the concentrations of chitosan, carboxymethyl inulin (CMI), and the drug on the response variables, i.e., particle size and percent entrapment efficiency of the mesalamine-loaded nanoparticle using the Box Behnken design (BBD). The correlation between the independent and dependent variables was investigated using the Design Expert generated mathematical equations, contour, and response surface designs.ResultAn optimized batch was developed using the ionotropic gel method with selected independent variables (A: + 1 level, B: 0 level, C: − 1 level) and the developed nanoparticles had a particle size of 184.18 nm, zeta potential 26.54 mV, and entrapment efficiency 88.58%. The observed responses were remarkably similar to the predicted values. The morphological studies revealed that the formulated nanoparticles were spherical, and the results of the FTIR and DSC studies indicated the drug-polymer compatibility. The nanoparticle showed less than 5% release in the pH 1.2. In the colonic region (pH 7.4), more than 80 % of the medication was released after 24 h. The kinetics study showed that the Higuchi and Korsemeyer-Peppas models had R2 values of 0.9426 and 0.9784 respectively, for the developed formulation indicating linearity, as revealed by the plots. This result justified the sustained release behavior of the formulation.ConclusionThe mesalamine-loaded chitosan-CMI nanoparticle has been successfully developed using the ionotropic gelation method. The nanoparticles developed in this study were proposed to deliver the drug to its desired site. The developed nanoparticles were likely to have a small particle size with positive zeta potential and high percent drug entrapment. It could be stated from the results that BBD can be an active way for optimizing the formulation and that nanoparticles can be a potential carrier for delivering therapeutics to the colon.

CELLULOSE ACETATE FLOATING MICROSPHERES OF METFORMIN HYDROCHLORIDE: FORMULATION AND CHARACTERIZATION

In this study, floating microspheres of metformin hydrochloride were prepared by using cellulose acetate polymer by solvent evaporation method. Four formulations were prepared by varying the ratio of drug and polymer. The prepared microspheres were then subjected to various evaluation parameters such as drug content, micromeritic evaluations, FTIR, SEM, floatability and in vitro dissolution study. Formulation F1 (1:1 ratio of polymer and drug) showed the highest drug release and drug content with good flow properties. The cumulative percentage of drug release significantly decreased with decreasing drug concentration with a constant polymer ratio. Scanning Electron Microscopy images of all formulations showed that the prepared floating microspheres were irregular in shape, and the surface was found to be non- uniform and rough. In vitro release studies indicated the mechanism of the drug release to follow the Korsemeyer-Peppas model, and “n” value was found to be between 0.54-1.89, indicating anomalous transport mechanism.

Exploring the Potentials of Corn Fiber Gum in Fabricating Mucoadhesive Floating Tablet of Poorly Gastro-retainable Drug.

To formulate and preliminary evaluated polysaccharide based mucoadhesive floating tablets of Cinnarizine. Gastro-retentive drug delivery systems has proved to be a successful approach to enhance the gastric residence with site specific targeting for achieving local or generalized effect. Various patents has also been filed globally employing gastro-retentive approach. The study is designed to explore the mucoadhesive and low density characteristics of corn fibre gum (CFG) for preparation of gastro-retentive floating tablets of cinnarizine. Floating tablets were prepared by direct compression technique using different concentrations of CFG (45, 50, 60% w/w). The formulated floating tablet batches were evaluated for their hardness, friability, drug content, floating duration/ lag time, swelling behavior, bioadhesive strength and in vitro drug release. Mucoadhesive strength was found to increase with an increment in the polysaccharide concentration. Swelling index was found to increase both with the increase in CFG concentration and with duration for which tablet remains in medium. The in vitro drug release studies indicated decrease in drug release (91% to 77%) with the increase in polymer concentration. The release data was further fitted to various kinetic models which revealed the drug release to be in accordance with Zero-order and Higuchi models, indicating polymer to exhibit the swellable matrix forming abilities. The value of n (between 0.458 and 0.997) from Korsemeyer Peppas model depicted the possibility of drug to follow more than one mechanism of release from the formulation i.e. diffusion and erosion. Stability studies revealed the preparations to retain their integrity and pharmaceutical characteristics at variable storage conditions. Thus from the research findings, CFG could be concluded to possess potential binder, release retardant and mucoadhesive characteristics which could be successfully employed for the formulation of gastro-retentive floating tablets.