Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.
The current study inspects the screening of the formulation components further, evaluates the physicochemical properties of the nanostructured lipid carriers (NLCs) for the antihypertensive drug as Candesartan Cilexetil (CC). The sequence screening of all excipients required for the preparation of NLCs should be performed. Firstly, the solubility of CC in different solid and liquid lipids is the major parameter for the selection of the best one. Precirol® ATO 5, Compritol ® 888 ATO and Glyceryl Monostearate (GMS) were showed the maximum solubility of the CC (1000±4.12 mg, 1500±4.15 mg and 1750±3.16 mg), respectively. Hence, they were selected as the solid lipids for the development of NLCs. Liquid lipids Transcutol® HP (30±2.21 mg/ml), Labrasol® ALF (25±1.32 mg/ml) and CapryolTM 90 (18±1.34 mg/ml) were observed to have good affinity for the drug on systematic screening of different liquid lipids. However, Precirol® ATO 5 was found to has good physical compatibility with Transcutol® HP, Compritol ATO 888 was found to has high physical miscibility with Labrasol® ALF and last GMS was appeared in good affinity and compatibly with CapryolTM 90. Hence, the following binary lipid mixtures (Precirol® ATO 5 - Labrasol® ALF), (Compritol® 888 ATO-Transcutol® HP) and (GMS - CapryolTM 90) were selected for the preparation of NLCs. The liquid–solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (55-59 0C). Lutrol F-68, Lutrol F-127, Cremophore EL and Cremophore® RH. In addition to, the combination of (Lutrol® F68:Cremophore® EL) and (Lutrol® F127: Cremophore® RH) were selected as the main surfactants for the preparation of NLCs formulations because of its good emulsification efficacy and homogeneity for the solid-liquid lipid mix. The prepared formulations were investigated for the different quality issues. All designed formulations observed in nanometer size of particles ranged from (408.9±11.5 to 114.6±8.3 nm) with high encapsulation efficiency around 99%. Also, the obtained results revealed that the ZP of the various formulations was consistently negative surface charge in between ((-13 ±2.3 to27.3±3.7 mV). Finally, formula number nine of CC (CC-NLC9) which composed of GMS (solid lipid), CapryolTM 90 (liquid lipid) and Lutrol® F127: Cremophore® RH (surfactants combination) was selected as the best formulation after the rank order for further investigations in the next work. Peer Review History: 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 Average Peer review marks at initial stage: 5.0/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Name: Dr. Mohammed Abdel-Wahab Sayed Abourehab Affiliation: Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia E-mail: maabourehab@uqu.edu.sa Name: Dr. Maha Khalifa Ahmed Khalifa Affiliation: Al-Azhar Universit - Cairo, Egypt E-mail: mahakhalifa.ahmed@hotmail.com Name: Dr. Evren Alğin Yapar Affiliation: Turkish Medicines and Medical Devices Agency, Turkiye E-mail: evren.yapar@yahoo.com Comments of reviewer(s): Similar Articles: FORMULATION AND CHARACTERIZATION OF TOPICAL NANO EMULGEL OF TERBINAFINE A REVIEW ON GOLD NANOPRTICLES SYNTHESIS AND CHARACTERIZATION FORMULATION AND EVALUATION OF ELASTIC LIPOSOMES OF DECITABINE PREPARED BY ROTARY EVAPORATION METHOD
Objectives: The aim of the study was to develop a proniosomal carrier system that is capable of efficiently delivering entrapped glimepiride over an extended period of time for the treatment of type 2 diabetes. Methods: Proniosomal gels were developed based on span 60 with and without cholesterol. The entrapment efficiency of drug inside niosomes developed from hydration of the proniosomes gel was also characterized. The in vitro release and skin permeation of glimepiride from various proniosomes gel formulations were investigated. The stability studies were performed at 4°C and at room temperature. Results: The maximum entrapment efficiency was obtained when the cholesterol concentration was 10% of total lipid (90.02%). In vitro release through mixed cellulose ester membrane showed sustained release of drug from proniosomes gels. In vitro drug permeation across rabbit skin revealed improved drug permeation and higher transdermal flux with proniosomes gels compared to hydro-alcoholic gel of drug. Also, good physical stability was also achieved with proniosomes gels. Kinetics of in vitro skin permeation showed diffusion model of drug release from formulations. Conclusion: The study proved that the concentration of cholesterol had great influence on the properties of proniosomes gels. Hence, proniosomes preparation containing 10% cholesterol can significantly increase trans-epidermal flux and prolong the release of glimepiride. Cite this article-Elsaied EH, Dawaba HM, Ibrahim EA, Afouna MI. Investigation of proniosomes gel as a promising carrier for transdermal delivery of Glimepiride.
Objective: The objective of this current study is to fabricate ocuserts to control the drug release from chosen bioadhesive polymeric matrixes to enhance patient compliance. Ciprofloxacin HCl (CFX HCl) was selected as a model drug.Methods: Different bioadhesive polymers with different film forming capabilities namely Hydroxy Propyl Methyl Cellulose (HPMC K4M), Poly Vinyl Alcohol (PVA), Sodium Carboxy Methyl Cellulose (Na CMC), Hydroxy Propyl Cellulose (HPC), Sodium Alginate (Na Alg.), pullulan and Xanthan Gum (XG) in different ratios were used in fabricating ocuserts using solvent-casting technique. Propylene Glycol (PG) was used as a plasticizer to facilitate the fabrication process. Characterization tests of the developed ocuserts were performed as well as bioadhesive tests and in vitro release studies of the incorporated drug. The obtained results were analysed using different release kinetic models. Stability of the selected ocuserts was investigated at 40±0.5 °C and 75±5% Relative Humidity (RH) for three months’ storage period. In vivo ocular irritation test was performed to investigate the safety of the formula in rabbits’ eyes as well as to test the release profile and thus to estimate In vitro In vivo correlation.Results: All the prepared ocuserts showed the uniformity of film characterization and bioadhesion strength ranged from 240±66 and 158±52dyne/cm2. Selected formula from the in vitro release study tested for in vivo study showed the slow release of ciprofloxacin drug up to 24 h with no signs of eye irritancy. Results for In vitro In vivo correlation showed an excellent correlation with R2 value of 0.9982.Conclusion: PVA based ocuserts proven to be a promising once-daily, effective and safe ocular delivery system of the drug.
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