scholarly journals FORMULATION AND EVALUATION OF ALGINATE-BASED MUCOADHESIVE BUCCAL PATCH FOR DELIVERY OF ANTIMIGRAINE DRUG

2018 ◽  
Vol 11 (4) ◽  
pp. 185 ◽  
Author(s):  
Gyati Shilakari Asthana ◽  
Sumit Sharma ◽  
Abhay Asthana
Keyword(s):  
Sodium Alginate ◽  
Drug Transport ◽  
Relative Bioavailability ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Average Weight ◽  
Lauryl Sulfate ◽  
Sumatriptan Succinate

 Objective: The present work was aimed with enhancement of oral bioavailability of sumatriptan succinate by sodium alginate-based mucoadhesive buccal patches.Methods: These patches were prepared by solvent-casting method using different concentrations of sodium alginate along with HPMC 5cps and maltodextrin as a film-forming polymer. Propylene glycol, sodium lauryl sulfate, and mannitol were used as plasticizer, penetration enhancer, and filler, respectively. Prepared patches were evaluated with respect to various in vitro parameters and in vivo studies were conducted on white strain New Zealand rabbits of either sex with average weight 2–3 kg.Results: All the formulations were transparent and homogeneous. F7 formulation containing Na alginate (250 mg), maltodextrin (250 mg), and HPMC 5cps (250 mg) displayed maximum folding endurance, mucoadhesive force, in vitro drug transport, and drug release and found to be stable up to 2 months in storage conditions. The pharmacokinetic parameters such as Cmax, tmax, and AUC were calculated from the data collected after in vivo studies. Sumatriptan succinate containing buccal patch displayed almost 1.73 folds and 2 folds higher Cmax and AUC, respectively, than plain drug solution. 1.93% of relative bioavailability was reported with the formulation.Conclusion: The outcome of the present work reveals that sumatriptan succinate-based mucoadhesive buccal formulation can improve overall performance of drug molecule in vitro and in vivo.

scholarly journals Sustained In Vitro and In Vivo Delivery of Metformin from Plant Pollen-Derived Composite Microcapsules

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1048
Author(s):  
Noha M. Meligi ◽  
Amro K.F. Dyab ◽  
Vesselin N. Paunov
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phoenix Dactylifera ◽  
Relative Bioavailability ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Sprague Dawley

We developed a dual microencapsulation platform for the type 2 diabetes drug metformin (MTF), which is aimed to increase its bioavailability. We report the use of Lycopodium clavatum sporopollenin (LCS), derived from their natural spores, and raw Phoenix dactylifera L. (date palm) pollens (DPP) for MTF microencapsulation. MTF was loaded into LCS and DPP via a vacuum and a novel method of hydration-induced swelling. The loading capacity (LC) and encapsulation efficiency (EE) percentages for MTF-loaded LCS and MTF-loaded DPP microcapsules were 14.9% ± 0.7, 29.8 ± 0.8, and 15.2% ± 0.7, 30.3 ± 1.0, respectively. The release of MTF from MTF-loaded LCS microcapsules was additionally controlled by re-encapsulating the loaded microcapsules into calcium alginate (ALG) microbeads via ionotropic gelation, where the release of MTF was found to be significantly slower and pH-dependent. The pharmacokinetic parameters, obtained from the in vivo study, revealed that the relative bioavailability of the MTF-loaded LCS-ALG beads was 1.215 times higher compared to pure MTF, following oral administration of a single dose equivalent to 25 mg/kg body weight MTF to streptozotocin (STZ)-induced diabetic male Sprague-Dawley rats. Significant hypoglycemic effect was obtained for STZ-induced diabetic rats orally treated with MTF-loaded LCS-ALG beads compared to control diabetic rats. Over a period of 29 days, the STZ-induced diabetic rats treated with MTF-loaded LCS-ALG beads showed a decrease in the aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides, cholesterol, and low-density lipoprotein-cholesterol (LDL-C) levels, as well as an increase in glutathione peroxidase (GPx) and a recovery in the oxidative stress biomarker, lipid peroxidation (LPx). In addition, histopathological studies of liver, pancreas, kidney, and testes suggested that MTF-loaded LCS-ALG beads improved the degenerative changes in organs of diabetic rats. The LCS-ALG platform for dual encapsulation of MTF achieved sustained MTF delivery and enhancement of bioavailability, as well as the improved biochemical and histopathological characteristics in in vivo studies, opening many other intriguing applications in sustained drug delivery.

scholarly journals Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technology

2009 ◽  
Vol 59 (1) ◽  
pp. 15-30 ◽  
Author(s):  
Pramod Kumar ◽  
Sanjay Singh ◽  
Brahmeshwar Mishra
Keyword(s):  
Drug Release ◽  
Extended Release ◽  
Relative Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Healthy Human ◽  
Tramadol Hydrochloride ◽  
Release Formulation ◽  
Extended Release Formulation

Development and biopharmaceutical evaluation of extended release formulation of tramadol hydrochloride based on osmotic technologyExtended release formulation of tramadol hydrochloride (TRH) based on osmotic technology was developed and evaluated. Target release profile was selected and different variables were optimized to achieve it. Formulation variables such as the level of swellable polymer, plasticizer and the coat thickness of semipermeable membrane (SPM) were found to markedly affect drug release. TRH release was directly proportional to the levels of plasticizer but inversely proportional to the levels of swellable polymer and coat thickness of SPM. Drug release from developed formulations was independent of pH and agitation intensity but dependent on osmotic pressure of the release media.In vivostudy was also performed on six healthy human volunteers and various pharmacokinetic parameters (cmax,tmax,AUC0-24,MRT) and relative bioavailability were calculated. Thein vitroandin vivoresults were compared with the performance of two commercial TRH tablets. The developed formulation provided more prolonged and controlled TRH release compared to the marketed formulation.In vitro-in vivocorrelation (IVIVC) was analyzed according to the Wagner-Nelson method. The optimized formulation (batch IVB) exhibited good IVIV correlation (R= 0.9750). The manufacturing procedure was found to be reproducible and formulations were stable over 6 months of accelerated stability testing.

scholarly journals Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 21 ◽  
Author(s):  
Yumei Lian ◽  
Xuerui Wang ◽  
Pengcheng Guo ◽  
Yichen Li ◽  
Faisal Raza ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Sodium Alginate ◽  
Primary Liver Cancer ◽  
Tumor Therapy ◽  
Average Particle Size ◽  
In Vivo Studies ◽  
Average Particle ◽  
Promising Alternative

Arsenic trioxide (ATO) has a significant effect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side effects. Considering these problems, red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) were developed to relieve the toxicity of ATO while maintaining its efficacy. ATO-loaded sodium alginate nanoparticles (SA-ATO-NPs, SANs) were prepared by the ion crosslinking method, and then RBCM was extruded onto the surface to obtain RSANs. The average particle size of RSANs was found to be 163.2 nm with a complete shell-core bilayer structure, and the average encapsulation efficiency was 14.31%. Compared with SANs, RAW 264.7 macrophages reduced the phagocytosis of RSANs by 51%, and the in vitro cumulative release rate of RSANs was 95% at 84 h, which revealed a prominent sustained release. Furthermore, it demonstrated that RSANs had lower cytotoxicity as compared to normal 293 cells and exhibited anti-tumor effects on both NB4 cells and 7721 cells. In vivo studies further showed that ATO could cause mild lesions of main organs while RSANs could reduce the toxicity and improve the anti-tumor effects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and effectively.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

FORMULATION, OPTIMIZATION AND EVALUATION OF MOXIFLOXACIN HYDROCHLORIDE GASTRO RETENTIVE TABLETS

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (01) ◽  
pp. 79-84
Author(s):  
Raghavendra K. Gunda ◽  
◽  
A. Vijayalakshmi ◽  
K. Masilamani ◽  
◽  
...  
Keyword(s):  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Wet Granulation ◽  
Statistical Parameters ◽  
Compression Technique ◽  
Ich Guidelines ◽  
Gastro Retentive

The objective of the current study was to develop gastro retentive formulation of moxifloxacin. HCl using various drug release modifiers and performing in vitro and in in vivo evaluations. Moxifloxacin is a novel synthetic fluoro quinolone antibacterial agent. Floating, muco adhesive tablets of moxifloxacin. HCl were prepared using variable amounts of HPMCK100M, Lannea coromandelica gum by direct compression technique and wet granulation technique, respectively. Formulations were developed, optimized and checked for pharmacopoeial tests. Results show that all the batches lie within the standard limits. Dissolution parameters of all formulations were sy=ubjected to kinetic fitting and various statistical parameters were determined. Formulation (FS5 ) containing 50 mg of HPMCK100M and 50 mg of LCG, is the best formulation showing similarity f2 =71.734, f1 = 4.271 with the marketed product (Avelox). It follows Higuchi's kinetics, non-fickian diffusion first order kinetics(n=0.717). In vivo studies were performed for the FS5 with 6 healthy rabbits and pharmacokinetic parameters were determined, compared with Avelox and it was found that FS5 produced similar results. Stability studies were performed for FS5 as per ICH guidelines. Results were found to be satisfactory. FS5 is expected to improve patient compliance by means of providing good clinical outcome

scholarly journals Preparation and in vivo evaluation of a gel-based nasal delivery system for risperidone

2016 ◽  
Vol 66 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Fugen Gu ◽  
Weina Ma ◽  
Gendalai Meng ◽  
Chunzhi Wu ◽  
Yi Wang
Keyword(s):  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Oral Drug ◽  
Pharmacokinetic Parameters ◽  
In Vivo Evaluation ◽  
Fast Absorption ◽  
Maximal Plasma ◽  
Vitro Effect

Abstract The aim of this study was to prepare a nasal gel of risperidone and to investigate the pharmacokinetics and relative bioavailability of the drug in rats. Compared with oral dosing, the risperidone nasal gel exhibited very fast absorption and high bioavailability. Maximal plasma concentration (cmax) and the time to reach cmax (tmax) were 15.2 μg mL-1 and 5 min for the nasal gel, 3.6 μg mL-1 and 30 min for the oral drug suspension, respectively. Pharmacokinetic parameters such as tmax′, cmax and AUC of oral and nasal routes were significantly different (p < 0.01). Relative bioavailability of the drug nasal preparation to the oral suspension was up to 1600.0 %. Further, the in vitro effect of the risperidone nasal gel on nasal mucociliary movement was also investigated using a toad palate model. The risperidone nasal formulation showed mild ciliotoxicity, but the adverse effect was temporary and reversible.

scholarly journals Preparation, characterization, and in vivo pharmacokinetics of thermosensitive in situ nasal gel of donepezil hydrochloride

2020 ◽  
Vol 70 (3) ◽  
pp. 411-422 ◽  
Author(s):  
Fugen Gu ◽  
Huimin Fan ◽  
Zhixin Cong ◽  
Shuang Li ◽  
Yi Wang ◽  
...  
Keyword(s):  
Ph Value ◽  
Relative Bioavailability ◽  
Nasal Delivery ◽  
Poloxamer 407 ◽  
Nasal Administration ◽  
Pharmacokinetic Parameters ◽  
Donepezil Hydrochloride

AbstractDonepezil hydrochloride thermosensitive in situ gel for nasal delivery was prepared by using Poloxamer 407 and Poloxamer 188 as thermoreversible polymers, hydroxypropyl-β-cyclodextrin and ethylparaben as permeation enhancer and preservative, respectively. The gelation temperature and time, pH value of the gel formulation were found to meet the requirements for nasal administration. The in vitro erosion and in vitro release tests exhibited obvious drug sustained release behavior. Meantime, main pharmacokinetic parameters such as tmax, cmax and AUC in plasma as well as in brain were significantly different between the nasal gel formulation and intragastric drug solution in rats (p < 0.01). The relative bioavailability and drug targeting efficiency of the gel formulation were calculated to be 385.6 and 151.2 %, respectively. Thus, the drug gel formulation might be a potential new delivery system for treatment of Alzheimer’s disease due to its higher bioavailability and better distribution to brain when compared to oral route.

Pharmacokinetics of Darolutamide, its Diastereomers and Active Metabolite in the Mouse: Response to Saini NK et al. (2020)

2020 ◽  
Vol 14 ◽  
Author(s):  
Pirjo Nykänen ◽  
Timo Korjamo ◽  
Hille Gieschen ◽  
Christian Zurth ◽  
Mikko Koskinen
Keyword(s):  
Protein Binding ◽  
Equilibrium Dialysis ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Tissue Samples ◽  
High Protein Binding ◽  
Mouse Hepatocytes ◽  
Mouse Response

Background: Saini et al. recently investigated the pharmacokinetics of darolutamide and its diastereomers in vitro and in vivo in Balb/c mice, reporting higher levels of (S,S)-darolutamide than (S,R)-darolutamide following intravenous or oral dosing, and interconversion of (S,R)-darolutamide to (S,S)-darolutamide. Objective: To present our in vitro and in vivo studies of darolutamide pharmacokinetics in mice, which contrast with the findings of Saini et al. Methods: Nude male Balb/c mice were orally dosed for 7 days with 25, 50, or 100 mg/kg of darolutamide twice daily. Pharmacokinetic parameters in plasma and tissue samples were assessed by liquid chromatography-tandem mass spectrometry. Metabolism and interconversion of darolutamide and diastereomers was investigated in cryopreserved Balb/c mouse hepatocytes. Protein binding was determined in plasma samples by equilibrium dialysis. Results and Discussion: At day 7, Cmax was reached 30 min after last dose. Rapid formation and greater exposure of ketodarolutamide versus darolutamide were observed. Plasma exposure of (S,R)-darolutamide was 3–5-fold higher than that of (S,S)-darolutamide. The fraction of unbound keto-darolutamide was almost 6-fold lower than for darolutamide. In mouse hepatocytes, conversion of (S,S)- to (S,R)-darolutamide was observed but conversion of (S,R)- to (S,S)- darolutamide was not detectable. Back-formation of keto-darolutamide to both diastereomers occurred at low levels. Conclusion: The darolutamide diastereomer ratio changes upon administration in mice and other species, due to interconversion through keto-darolutamide. This is not considered clinically relevant since both diastereomers and ketodarolutamide are pharmacologically similar in vitro. Based on the high protein binding of keto-darolutamide, its contribution in vivo in humans is considered low.

scholarly journals Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4604
Author(s):  
Rajveer Singh ◽  
Anupam Gautam ◽  
Shivani Chandel ◽  
Arijit Ghosh ◽  
Dhritiman Dey ◽  
...  
Keyword(s):  
In Silico ◽  
Inhibitory Effect ◽  
Polyphenolic Compounds ◽  
Host Protein ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Post Translational Modification ◽  
In Silico Studies

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.

scholarly journals ORAL DELIVERY OF ZOLMITRIPTAN LOADED FAST DISINTEGRATING FILM: FORMULATION DEVELOPMENT, STATISTICAL OPTIMIZATION, IN-VITRO AND IN-VIVO EVALUATION

2019 ◽  
pp. 13-22 ◽  
Author(s):  
Iti Chauhan ◽  
Mohammad Yasir ◽  
Madhu Verma
Keyword(s):  
Oral Delivery ◽  
Stability Study ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Albino Rats ◽  
Formulation Development ◽  
In Vivo Evaluation ◽  
Disintegration Time

Introduction: Fast dissolving film technology has been developed out as a alternative drug delivery system that gives an exception advantage for taking medications. Objective: The aim of this study was to formulate and evaluate the Zolmitriptan loaded fast disintegrating oral film by solvent casting method. Material and methods:  A preliminary study was conducted to select a suitable film forming polymer and plasticiser concentration.The formulation was optimized with the help of 22 factorial designs in which polymer and plasticizer concentration at two levels was taken as independent factors and disintegration time, tensile strength and % elongation were taken as dependent factors. The optimized formulation OP1 was subjected to stability study as per the ICH guidelines at 40 ± 0.50C / 75 ± 5% RH for six months. In vivo studies were conducted on Wister albino rats and concentration of drug in blood was analysed by HPLC technique. Various pharmacokinetic parameters for OP1 were determined and compared with reference formulation (drug sol.). Result and Discussion: For optimized formulation various parameters were found to be in acceptable range and it was stable under specified conditions. The value of AUC0–t (ng h/ml), AUC0–∞ (ng h/ml) of the OP1 was found to be 723.91± 84.21, 770.90 ± 104.32, respectively, for the drug sol 468.56 ± 79.36, 500.37 ± 95.43 respectively. Relative bioavailability of OP1 was 1.55 time than that of drug sol. Conclusion: The formulation not only increases the bioavailability of drug but also produce the quick action for the migraine patients. 

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