Cumulative Percentage Drug Release Research Articles

Design and Development of Resveratrol NLCs and their Role in Synaptic Transmission of Acetylcholine in C. elegans Model

Background: The damage of synapses and neurons leads to the cognitive impairment and this is the root cause of progression of Alzheimer’s disease. The nematode Caenorhabditis elegans is widely used as an in vivo model to study the synaptic transmission because of the relatively modest worm nervous system, which is like mammals. Objective: The aim of this work is to assess the effectiveness of resveratrol-loaded nanostructured lipid carrier for the management of Alzheimer's disease. Method: Resveratrol loaded nanostructured lipid carrier (RES-NLC) was prepared by modified solvent emulsification-diffusion technique, using compritol 888ATO (solid lipid), sesame oil (liquid lipid) and tween 80 (surfactant). Results: Formulations were characterized via particle size (155.08±3.28 nm), polydispersity index (PDI) (0.121), and zeta potential (-16.58). The entrapment efficiency was found to be 79.65±2.52% and cumulative percentage drug release was 63.54% up to 8 hours. Anticholinesterase inhibition competence was performed through Aldicarb assay. It was found that surge in the dose of RES-NLC caused an increased worm paralysis, which was credited to the accumulation of acetylcholine in synapses. Quantitative RT-PCR performed showed the effect of formulation on acetylcholinesterase (AChE) AChE 1 and AChE 2 genes. RES-NLC (dose 400 μg/ml) decreased the AChE 1 expression 3.23±0.13 fold whereas AChE 2 expression decreased 3.34±0.14 fold with the same dose. RES-NLC displayed transfer latency and escape latency of 27.50 ± 2.34 and 30.17 ± 2.82. Conclusion: Based on the results, it was concluded that RES-NLC was effective in increasing acetylcholine concentration in synapses and thus in the treatment of Alzheimer's disease. Keywords: Resveratrol, Alzheimer's disease, NLC, C. elegans, aldicarb assay, RT-PCR.

Formulation and Optimization of Nanosuspension Prepared By Media Milling Technique to Enhance the Solubility of Isradipine

Isradipine is a poorly water soluble antihypertensive drug has low bioavailability. The aim of this study was to formulate and characterize isradipine nanosuspension to enhance the solubility of isradipine and thus its bioavailability. Media milling technique was used for the formulation of nanosuspension. The effects of different important process parameters, i.e. the selection of stirring time, selection of concentration of zirconium beads, stirring speed were investigated by preliminary studies while concentration of stabilizers were optimized by simplex lattice design. Concentration of HPMC E3 LV(X1), Carbopol 934P(X2) and PVP K25(X3) were selected as the independent variables whereas mean particle size (Y1), saturation solubility (Y2) and cumulative percentage drug release (cpr) (Y3) were selected as dependent variables. The optimized batch had 100% w/v of zirconium beads, 0.5%w/v of PVP K25 as stabilizer, 0.1%w/v of isradipine, 15 ml of distilled water and 20 hours of stirring time. The particle size and zeta potential of optimized nanosuspension were 248.6 ± 20 nm and 13.96 ± 5 mV respectively. The size of particles of nanosuspension was measured by particle size analyser and transmission electron microscopy (TEM). Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) analysis indicated that there was no interaction between drug and stabilizers. The saturation solubility and in vitro dissolution rate of isradipine was significantly increased by particle size reduction and which may leads to increase the bio-availability of the Isaradipine. The stability study of the formulation was carried out for a period of 12 months.

DEVELOPMENT AND IN-VITRO EVALUATION OF MATRIX-TYPE TRANSDERMAL PATCHES OF LOSARTAN POTASSIUM

Objective: Since last decade drugs through skin has received great attention of many researchers. The aim of present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of Losartan potassium. Methods: Four transdermal patches formulations of Losartan potassium were prepared by using different polymers using blends of different polymers like polyvinylpyrrolidone K30 (PVP K30) and ethylcellulose (EC), hydroxypropyl methyl cellulose and chitosan. Physical studies including thickness, folding endurance moisture content, tensile strength and flatness were performed on all formulations. In-vitro diffusion study of 10 hrs was performed by means of Franz diffusion cell. Results: Thickness of four prepared patches lies in the range of 0.30 to 0.33 mm. Percent moisture content was found to be in the range of 2.56 to 3.44. The cumulative percent drug release after 10 hrs in between 38.41 to 80.41%. Stability study performed on selective batch, TP1 for 12 weeks at different temperature indicates stability of transdermal patches at room temperature. Conclusion:Present study concluded that Losartan potassium can be formulated into the transdermal matrix type patches to sustain its release characteristics. Polymeric composition of batch TP1 (PVP K30: Chitosan: 70:30) was found to be the best choice for manufacturing transdermal patches of Losartan potassium among the formulations studied. Peer Review History: Received 2 April 2017; Revised 12 May; Accepted 13 May, Available online 15 May 2017 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Asmaa Ahmed Mohamed Ahmed Khalifa, Pharos University, Alexandria, Egypt, asmaa.khalifa@pua.edu.eg Dr. Dalia Kamal Zaffar Ali, Modern University for technology and information, Egypt, dr.moda88@gmail.com Similar Articles: DEVELOPMENT AND EVALUATION OF MATRIX TYPE TRANSDERMAL PATCHES OF PIOGLITAZONE HYDROCHLORIDE

Transdermal potential and anti-gout efficacy of Febuxostat from niosomal gel

Gout is a metabolic disorder which causes inflammation of the joints. The pain can be relieved by taking anti-inflammatory or pain-relieving medication. Febuxostat, a xanthine oxidase inhibitor is also used in the treatment of gout. It is a weak acid (pKa = 3.08) and is therefore, practically insoluble in water. Due to its limited solubility in water and susceptibility to enzymatic degradation in intestine and liver, its oral bioavailability is affected. The presence of food also decreases its maximum plasma concentration (Cmax) by 38–39%. Hence, transdermal route is preferred for its administration. In the present research, niosomal vesicles were selected for Febuxostat delivery because of their penetration enhancing ability. Niosomes containing Febuxostat were prepared using thin film hydration method. A 23 factorial design (DOE analysis) was carried out to reduce the number of experiments. Parameters contribution was determined using a 3-D response curve. Prepared optimized batch (F4) exhibited entrapment efficiency of 73.93 ± 0.75% and percent cumulative drug release of 83.03 ± 0.07%. Transmission Electron Microscopy (TEM) revealed vesicular, spherical particles with a smooth surface in the nano range. Niosomal gel of optimized batch (F4) was prepared incorporating 2% w/w carbopol 934. The ex-vivo permeation study was performed in the Franz diffusion apparatus using excised rat abdominal skin in phosphate buffer pH 7.4, which showed prolonged drug permeation of 80.37 ± 0.02%. In-vivo study of optimized Febuxostat niosomal gel NG (F4) on rabbits revealed better results than the standard (pure) Febuxostat. NG (F4) exhibited good stability throughout 90 days at different temperature and humidity.

DEVELOPMENT AND EVALUATION OF TRANSDERMAL GEL OF LORNOXICAM

Objective: Transdermal drug delivery systems deliver the drug through the skin at controlled rate to the systemic circulation. It maintains the blood concentration of the drug within the therapeutic system window ensuring that drug levels neither fall below the minimum effective concentration nor exceed the minimum toxic dose. The objective of the present work was to formulate transdermal gel of Lornoxicam. It is a COX-1 and COX-2 inhibitor used in the treatment of inflammation, pain and edema, rheumatoid arthritis. Methods: Transdermal gel of Lornoxicam was formulated using triethanolamine as solvent, HPMC K100 and EC as polymers. Formulated gel was evaluated with respect to different physiochemical parameters such as pH, viscosity, spreadability. In-vitro release study was performed for 10 hrs. Selected formulation was subjected to stability testing at different temperatures. Results: There was good homogeneity in all formulations and no lumps were present. The pH of the gel formulations was in the range of 6.77 to 7.14. Viscosity of various formulated gels was found in the range of 2176.5 to 3468.4 centipoises. The cumulative percent drug release after 10 hrs in between 50.3 to 82.11%. Accelerated stability studies for 12 weeks revealed that the transdermal gel formulation were stable at up to 45oC. Conclusion: Study concludes Lornoxicam can be delivered in the form of transdermal gel in an efficient way. On basis of drug content, particle size morphology, in-vitro release and stability studies, it can be concluded that formulation LTG4 was an optimum formulation. Peer Review History: Received 7 February 2017; Revised 11 March; Accepted 13 March, Available online 15 March 2017 Academic Editor: Dr. Amany Mohamed Alboghdadly, Princess Nourah bint abdulrahman university, Riyadh, amalbgadley@pnu.edu.sa UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 4.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Prof. Dr. Syamsudin Abdillah, Pancasila University, Indonesia, syamsudin.abdillah@gmail.com Noha El Baghdady, MTI University, Cairo, Egypt, nohasalah21@yahoo.com Similar Articles: INVESTIGATION OF PRONIOSOMES GEL AS A PROMISING CARRIER FOR TRANSDERMAL DELIVERY OF GLIMEPIRIDE

Evaluation of Novel Polymer in the Development of Floating In situ Gelling System

The objective of this work was to assess the new polymer obtained from natural source (Helianthus annuus) in the formation of floating in situ gel of Ranitidine HCl. Low Methoxy Pectin (LMP), calcium carbonate, sodium citrate, D-mannitol, methylparaben and propylparaben were utilized in developing floating in situ gelling formulations. The developed formulations were evaluated for various physicochemical properties like viscosity, floating lag time, and duration of floating, in vitro gelation and in vitro drug release. The 32 full factorial design was applied wherein concentration of LMP and calcium carbonate were considered as independent variables whereas floating lag time and drug release after 8 h (Q8 ) were taken as dependent variables. All formulations (F1–F9) exhibited floating within 60 s and remained floated for around 24 h. All the formulations were pourable before coming in contact with gastric fluid. It was seen that floating lag time and cumulative percentage drug release was influenced by concentration of LMP and calcium carbonate. Formulation F5 showed optimum floating lag time (37 s) and drug release after 8 h (98.09%) amongst developed in situ gels. Thus it can be concluded that Ranitidine HCl can be formulated as floating in situ gel using LMP as a gelling polymer to sustain the drug release for 8 h.

FORMULATION AND IN-VITRO EVALUATION OF FLOATING MICROBALLOONS OF STAVUDINE

Objectives: Objective of present study involves preparation and evaluation of floating microballoons of Stavudine. It is a potent antiviral agent, used for treatment of human immunodeficiency virus (HIV) infection. In present study Stavudine is used as a model drug, to increase its residence time in the stomach without contact with the mucosa. Methods: Eight floating microballoons formulations of Stavudine were prepared by using different polymers i.e. Eudragit S100, EC and PVP K30, in different ratio by emulsion solvent diffusion method. The microballoons were prepared by the emulsion solvent diffusion technique using different ratio of polymers (Eudragit S100, Ethyl cellulose and PVP K 30) as carriers. Results: The mean particle diameter of the microballoons was between 230.23-238.33µm.The yield of microballoons was up to 68.32-80.22%. The cumulative percent drug release after 24 hrs of the Stavudine microballoons was in the range of 53.62 to 87.45%. The mean percentage buoyancy of the microballoons was between 69.23-82.53%. The cumulative percent drug release after 24 hrs of the Stavudine microballoons was 53.62 to 87.45%. Conclusion: Stavudine floating microballoons formulations of batch MB4 was concluded as the optimum formulations among the all 8 formulations based on different parameters.Study concludes that stavudine can be delivered through floating microballoons dosage form in an effective way. Peer Review History: Article received on- 29 September; Revised on- 20 October; Accepted on- 5 November , Available online 15 November 2016 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia, Indonesia, ahmad.najib@umi.ac.id UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Michael Otakhor Erhunmwunse, St. Philomena Catholic Hospital, Nigeria, dedoctor4life@gmail.com Prof. Dr. Kapil Kumar, Global Institute of Pharmaceutical Education and Research, Kashipur, US Nagar, Uttarakhand, India, kapil5november@gmail.com Similar Articles: DEVELOPMENT AND EVALUATION OF IN SITU GELLING GASTRORETENTIVE FORMULATIONS OF MELOXICAM FORMULATION AND EVALUATION OF IBUPROFEN GASTRO-RETENTIVE FLOATING TABLETS DEVELOPMENT AND EVALUATION OF RITONAVIR HOLLOW MICROBALLOONS FOR FLOATING DRUG DELIVERY FORMULATION AND IN-VITRO EVALUATION OF FLOATING MICROBALLOONS OF STAVUDINE

FORMULATION AND EVALUATION OF ETODOLAC NIOSOMES BY MODIFIED ETHER INJECTION TECHNIQUE

Objectives: Niosomes are non-ionic surfactant based multilamellar or unilamellar vesicles with aqueous solution of solute that is enclosed by a membrane. Etodolac is an indole acetic acid derivative with half-life of 4 to 7hrs. It is used for the treatment of Rheumatoid arthritis. Whenever used orally, it has many systemic side effects, so it is not preferred orally. The aim of present study was to develop niosomes of Etodolac to avoid all drawbacks associated with it like first pass metabolism and side effects. Methods: In present study four niosomes formulations of Etodolac were successfully developed by modified ether injection technique using different nonionic surfactant i.e. Span 20, Span 40, Tween 20, Tween 40 and cholesterol. Formulations were evaluated for different parameters like particle size, entrapment efficiency, in-vitro release, stability studies. Results: Niosomes formulations of batch N3 shows maximum mean particle diameter i.e. 2.46 µm. The entrapment efficiency of the niosomes was between 66.52-78.32%. The entrapment efficiency was found to be higher with the batch N4 (78.32%). The cumulative percent drug release after 10 hrs of the Etodolac niosomes in between 40.59-78.55%. 68.5% for N1, 50.49% for N2, 40.59 for N3 and 78.55 for N4. Accelerated stability studies for 12 weeks revealed that the Etodolac niosomes formulations of batch N4 were stable at up to 450C. Conclusion: Study concludes that Etodolac can be delivered by niosomes dosage form effectively and all limitations associated with it can be avoided. Peer Review History: Article received on-16 September, Revised 24 October, Accepted 30 October, Available online 15 November 2016 UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file: Reviewer's Comments: Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Barkat Ali Khan, Kampala International University , Uganda, barki.gold@gmail.com Prof. Dr. Kapil Kumar, Global Institute of Pharmaceutical Education and Research, Kashipur, US Nagar, Uttarakhand, India, kapil5november@gmail.com Similar Articles: INVESTIGATION OF PRONIOSOMES GEL AS A PROMISING CARRIER FOR TRANSDERMAL DELIVERY OF GLIMEPIRIDE

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose.

OPTIMIZATION OF GASTROADHESIVE DELIVERY SYSTEM FOR NARROW ABSORPTION WINDOW DRUG USING NATURAL POLYMERS

A system comprising mechanisms of gastric retention by gastroadhesion has been investigated employing combination of hibiscus esculentus mucilage and xanthan gum for diltiazem hydrochloride. Various formulations of diltiazem hydrochloride were prepared by wet granulation technique using Box-Behnken approach and were tested for compatibility, swelling behaviour, in vitro drug release, mucoadhesive strength and accelerated stability. The percent cumulative drug release at 8th hr (Y1), time to release 80 % of drug (Y2), mucoadhesive strength (Y3) and mucoadhesive time (Y4) were used as the formulation responses in order to optimize the formulation. The accelerated stability studies revealed that the tablets retained their characteristics even after stressed storage conditions. The DLT mucoadhesive matrices were 49.99 mg hibiscus esculentus mucilage, 44.97 mg xanthan gum and 4.48 ton compression load fulfilled the optimal criteria of best sustained release rate and bioadhesive characteristics with t80% of 7.6 h, Q8h of 89.83 % and bioadhesive strength of 22.14 g.

Preparation and Characterization of Atenolol Laden Nanoparticles

In the present study, an attempt was made to develop nanoparticles of Atenolol for effective treatment of Glaucoma. By developing the nanoparticulated delivery the required action of drug at the target site i.e. at eye can be provided. The nanoparticles were prepared by nano precipitation method. The formulation was subjected to different evaluation parameters like particle size, zeta potential, drug content uniformity, entrapment efficiency, in-vitro drug release study. The particle size range of nanoparticles was found to be 100-256 nm. The zeta potential of nanoparticles was found to be 55.87 to 64.87 mV. The drug content of different formulations F1 to F8 was calculated and the content was found to be in range of 95.98 TO 102.14 %. The entrapment efficiency was found to be in range of 45.76 to 72.98%. From the in-vitro drug release studies, it was found that the cumulative percent drug release for optimised formulation F5 found to be between 12.56 to 88.15 % respectively.

Enhancement of Loperamide Dissolution Rate by Liquisolid Compact Technique.

Purpose: The aim of present study was to improve the dissolution rate of poorly soluble drug Loperamide (LPM) by liquisolid compact technique. Methods: Liquisolid compacts of LPM were prepared using Propylene glycol (PG) as a solvent, Avicel pH 102 as carrier, Aerosil as coating material and Sodium Starch Glycolate (SSG) as superdisintegrant. Interactions between the drug and excipients were examined by Fourier Transform Infrared (FTIR) spectroscopy. The dissolution studies for LPM liquisolid formulation, marketed product and pure drug were carried out in pH 1.2 HCl buffer as dissolution media. Results: Results confirmed the absence of chemical interactions between the drug and excipients. From the solubility studies, it was observed the LPM was highly soluble in PG thereby it was selected as a solvent. The dissolution efficiency of LPM at 15 min was increased from 9.99 % for pure drug and 54.57% for marketed product to 86.81% for the tablets prepared by liquisolid compact technique. Stability studies showed no significant change in percent cumulative drug release, hardness, disintegration time, friability and drug content for 3 months. Conclusion: Formulation F2 showed significant increase in dissolution rate compared to the marketed product at pH 1.2 where LPM is largely absorbed. Around 90% of the drug was released from F2 in 30 min compared to the marketed product and it might be due to the increased wetting and surface area of the particles. Hence, the liquisolid compact technique appears to be a promising approach for improving the dissolution rate of poorly soluble drug.

Application of factorial design approach in development and evaluation of self microemulsifying drug delivery system (SMEDDS) of mebendazole

Self microemulsifying drug delivery systems (SMEDDS) are defined as isotropic mixtures of natural or synthetic oils, surfactants and co-solvents/co-surfactants. Upon mild agitation followed by dilution in aqueous media, such as GI fluids, these systems can form fine oil in water o/w microemulsion. The purpose of this study was to formulate SMEDDS containing mebendazole. Labrafil M2125 CS (an oil), Tween 20 (a surfactant), and Maisine 35-1 (a cosurfactant) were used to formulate SMEDDS. Effect of concentrations of oil and surfactant on emulsification process and in vitro drug release (percent cumulative drug release) was studied using 32 factorial design. Multiple regression analysis data and response surfaces obtained showed that viscosity increased significantly with increasing amount of co-surfactant. Whereas, decrease in emulsification time, it may decreases average droplet size of resultant microemulsion and rapid drug release. The drug release from the formulation increased with increasing amount of surfactant concentration increases solubility of drug in system. Prepared SMEDDS produced acceptable properties of immediate-release dosage forms. The L5 formulation was found to be optimized on basis of high percent cumulative drug release. And it is evaluated by globule size and zeta potential indicates globule size is in micrometer range and good stable formulation. It may expect to increase the bioavailability of mebendazole as solubility enhances.

Spray-Dried Microspheres of Roxithromycin for Formulating into Dispersible Tablets Using Central Composite Design

The present investigation aims at development of spray-dried microspheres for formulation of roxithromycin dispersible tablets. The spray drying process was optimized using a central composite design to study the effect of two critical variables - amount of polymer Eudargit EPO® (X1) and inlet temperature (X2) on entrapment efficiency of drug and percentage cumulative drug release (% CDR). The maximum entrapment efficiency and % CDR was found at high values of inlet temperature and high level of polymer concentration. A drug entrapment efficiency of about 58.48 % (w/w), loading capacity of 64.22% (w/w), 94.26% CDR and particle size of 615 nm were achieved for the optimized batch RMS-3 of roxithromycin microspheres. ANOVA was applied to entrapment effeciency and % CDR to study the fitting and the significance of the model. The model estimated using present study has utility as response surface for cumulative percent of drug release from microspheres. The spray dried optimized microspheres were further formulated into dispersible tablets using direct compression method. The prepared tablets were evaluated for different parameters and the results obtained were found to be within the pharmacopoeial limits. The developed dispersible tablets showed better taste profile when compared with the marketed formulation and were found to be stable. Keywords: Central composite design, Eudragit® EPO, roxithromycin, spray drying, taste masking, microspheres, dispersible tablets.

Maximizing the Therapeutic Efficacy of Imatinib Mesylate–Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design

This research purposed to formulate an optimized imatinib mesylate (IM)–loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y1), zeta potential (Y2), entrapment capacity percentage (Y3), the percentage of initial drug release after 2 h (Y4), and the percentage of cumulative drug release after 24 h (Y5) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, −62.4 mV, 82.96%, 18.93%, and 89.45% for Y1, Y2, Y3, Y4, and Y5, respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach.

Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model

Purpose. Oxidative stress is the leading cause in the pathogenesis of Parkinson’s disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. Methods. In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box–Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson’s-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. Results. An optimized SNEDDS formulation consisting of Sefsol + vitamin E–Solutol HS 15–Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. Conclusion. Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in neurodegenerative disorders like Parkinson’s disease.

Development of transferosomal gel for trans-dermal delivery of insulin using iodine complex

The main object of this current research was to examine transferosomes as a transdermal delivery system for insulin, to overwhelm the difficulties related with its subcutaneous delivery. Transferosomal gel formulations were prepared by rotary evaporation sonication technique. The result revealed that insulin was successfully entrapped (78%) in optimized formulations (2.5 I.U. of the drug and 25% of sodium cholate) with cumulative percent drug release (83.11 ± 3.782). The glucose lowering study revealed that the transferosomal gel with chemical penetration enhancer showed better glucose lowering effect as compared to the control gel. Consequently, this study authenticated that the transferosomal gel can be used as a possible substitute to the conventional formulations of insulin with progressive permeation characteristics for transdermal application.

Natural Macromolecules in the Development of Safe and Effective Gastroretentive Floating Microparticles of Metformin Hydrochloride

Background: Metformin hydrochloride, an oral hypoglycaemic, shows better absorption from upper part of the gastric region. Natural/herbal substances have been investigated for the development of natural polymer-based drug delivery systems owing to the desirable properties like biodegradability, biocompatibility, aqueous solubility, swelling ability, easy availability and cost effectiveness. Method: Therefore, three natural macromolecules: Glycine max (soya chunks), Metroxylon sagu (sago starch) and Plantago ovata (psyllium husk) were used for developing its gastroretentive floating microparticles for expected improvement in bioavailability. The macromolecules and the prepared microparticles were evaluated for physicochemical properties, FTIR, XRPD, DSC and dug release. Result: The percent drug content was in the range of 60.353 ± 1.25 to 92.682 ± 2.47 % for all the microparticles. All the formulations showed good swelling and floating properties (the formulation prepared with P. ovata showed the best swelling and in vitro floatability). The FTIR studies showed that the herbal carriers were compatible with the drug. XRD and DSC studies showed a transition in the physical state of the drug in the formulations from crystalline state to amorphous state. In vitro drug release studies showed good percent cumulative drug release from all the formulations (72.13 to 87.06 % at the end of 6 hour) with non-fickian diffusion process. Conclusion: Therefore, it was concluded that the herbal macromolecules may be the potential, safe and effective carriers for improving the drug delivery of the metformin like drugs by developing, effective gastroretentive floating drug delivery systems.

Development and Statistical Optimization of Sustained Release Gastro Retentive Floating Tablets of Cephalexin

The aim of present study was to formulate the sustained release floating tablets of Cephalexin (CPL) by direct compression method and optimized by Box-behnken Response Surface Methodology (RSM). A computer aided optimization technique was employed to investigate the formulation design by Box-behnken RSM (Design Expert Software version 8.0.7.1) to study the effect of the concentration of various polymer blends on the property of CPL gastroretentive floating tablets like floating lag time (FLT), cumulative percent drug release (%CDR). The independent variables investigated were polymeric concentrations (X1) and dependent variables were FLT (Y1), %CDR (Y2) in 0.1N HCl buffer at the end of 8 h. Results from precompression evaluation indicated that all the 17 and optimized formulation F18 were complied with the pharmacopoeial limits. The predicted value for FLT and %CDR obtained from software was compared with the experimental value of FLT and %CDR of optimized formulation F-18 and it was observed that the obtained experimental value was in very close agreement with the predicted value. The optimized formulation (F-18) gave good FLT and %CDR when compared to the 17 formulations. Key words: Cephalexin: Design Expert Software; Floating tablets; Optimization; Response Surface Methodology.

DESIGN, CHARACTERIZATION AND EVALUATION OF MUCOADHESIVE NASAL IN SITU GELLING FORMULATIONS OF VENLAFAXINE HYDROCHLORIDE FOR BRAIN TARGETTING

The poor bioavailability and the therapeutic effectiveness exhibited by the anti-depressant venlafaxine hydrochloride on oral administration is overcome by the use of ion-activated gel forming systems that are instilled as drops; these undergo gelation in the nasal cavity. The present study describes the design, characterization and evaluation of mucoadhesive nasal in situ gelling drug delivery of venlafaxine hydrochloride using different polymers like sodium alginate, HPMC and pectin in various concentrations. DSC studies revealed compatibility of the drug and excipients used. The in situ gels were characterized for physicochemical parameters, gelling ability, rheological studies, drug content, drug entrapment efficiency, in vitro mucoadhesive strength, water holding capacity, gel expansion coefficient and in vitro drug release studies. The amount of polymer blends was optimized using 23 full factorial design. The influence of experimental factors on percentage cumulative drug release at the end of 2 and 8 hours were investigated to get optimized formulation. The responses were analyzed using ANOVA and polynomial equation was generated for each response using multiple linear regression analysis. Optimized formulation, F9, containing 1.98% w/V sodium alginate, 0.64% w/V hydroxylpropyl methylcellulose, 0.99% w/V pectin showed percentage cumulative drug release of 19.33 and 80.44 at the end of 2 and 8 hours, respectively, which were close to the predicted values. The optimized formulation was subjected to stability study for three months at 300C /75% RH. The stability study revealed no significant change in pH, drug content and viscosity. Thus, venlafaxine hydrochloride nasal mucoadhesive in situ gel could be successfully formulated to improve bioavailability and to target the brain.