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.

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 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.

FORMULATION AND IN-VITRO EVALUATION OF ZOLMITRIPTAN IN SITU GEL FOR NASAL ADMINISTRATION

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (12) ◽  
pp. 54-58
Author(s):  
P. H Patil ◽  
◽  
V. S Belgamwar ◽  
D. A Patel ◽  
S. J. Surana
Keyword(s):  
Evaluation Studies ◽  
Methyl Cellulose ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Histopathological Study ◽  
In Situ Gel ◽  
In Vitro Evaluation ◽  
Effective Delivery

The aim of present investigation was formulation and in-vitro evaluation of in situ gel for the nasal delivery of zolmitriptan. The in situ gel was prepared by temperature induced gelation technique using Pluronic with mucoadhesive polymer hydroxy propyl methyl cellulose K4 M in different ratios. The in situ gels so prepared were characterized and from the evaluation studies, batch PH2 was optimized and further subjected for stability studies at 30±2°C and 60±5% RH for 90 days. These formulations retained good stability at accelerated conditions and also did not show any remarkable damage to nasal mucosa in histopathological study. Owing to these properties it can be used as an effective delivery system for the nasal route.

scholarly journals Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1157
Author(s):  
Ali M. Nasr ◽  
Sameh S. Elhady ◽  
Shady A. Swidan ◽  
Noha M. Badawi
Keyword(s):  
Fatty Alcohol ◽  
Desirability Function ◽  
Area Under The Curve ◽  
Free Form ◽  
Pharmacokinetic Parameters ◽  
Anticancer Efficacy ◽  
Cox 2

Introduction: Several recent studies have shown that the role of cyclooxygenase 2 (COX-2) in carcinogenesis has become more evident. It affects angiogenesis, apoptosis, and invasion, and plays a key role in the production of carcinogens. It has also been reported that COX-2 inhibitors such as celecoxib (CLX) might play an effective role in preventing cancer formation and progression. Formulation of CLX into nanovesicles is a promising technique to improve its bioavailability and anticancer efficacy. Aim: The aim of this study is to optimize and evaluate the anticancer efficacy of CLX-loaded in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles in-vitro and determine its pharmacokinetic parameters in-vivo. Methods: The novel provesicular powders were prepared by the slurry method and optimized by 32 full factorial design using the desirability function. Results: Small mean particle size was achieved by the formed vesicles with value of 351.7 ± 1.76 nm and high entrapment efficacy of CLX in the formed vesicles of 97.53 ± 0.84%. Solid state characterization of the optimized formulation showed that the powder was free flowing, showed no incompatibilities between drug and excipients and showed smooth texture. The cytotoxic study of the optimized formula on HCT-116, HepG-2, A-549, PC-3 and MCF-7 cell lines showed significant increase in activity of CLX compared to its free form. The pharmacokinetic study on albino rabbits after oral administration showed significant increase in the area under the curve (AUC)0–24 h and significantly higher oral relative bioavailability of the optimized formulation compared to Celebrex® 100 mg market product (p < 0.05). Conclusion: All findings of this study suggest the potential improvement of efficacy and bioavailability of CLX when formulated in the form of in-situ provesicular powder composed of surfactants and fatty alcohol-based novel nanovesicles for its repositioned use as an anticancer agent.

scholarly journals Selective targeting of the TLR2/MyD88/NF-κB pathway reduces α-synuclein spreading in vitro and in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Debashis Dutta ◽  
Malabendu Jana ◽  
Moumita Majumder ◽  
Susanta Mondal ◽  
Avik Roy ◽  
...  
Keyword(s):  
Lewy Bodies ◽  
Selective Inhibition ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Interaction Domain ◽  
Selective Targeting ◽  
Nemo Binding Domain ◽  
Microglial Inflammation

AbstractPathways to control the spreading of α-synuclein (α-syn) and associated neuropathology in Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) are unclear. Here, we show that preformed α-syn fibrils (PFF) increase the association between TLR2 and MyD88, resulting in microglial activation. The TLR2-interaction domain of MyD88 (wtTIDM) peptide-mediated selective inhibition of TLR2 reduces PFF-induced microglial inflammation in vitro. In PFF-seeded A53T mice, the nasal administration of the wtTIDM peptide, NEMO-binding domain (wtNBD) peptide, or genetic deletion of TLR2 reduces glial inflammation, decreases α-syn spreading, and protects dopaminergic neurons by inhibiting NF-κB. In summary, α-syn spreading depends on the TLR2/MyD88/NF-κB pathway and it can be reduced by nasal delivery of wtTIDM and wtNBD peptides.

scholarly journals Temperature-dependent in Situ Gel of Clotrimazole: an Experimental Study

Folia Medica ◽  
2019 ◽  
Vol 61 (2) ◽  
pp. 266-276
Author(s):  
Vipul P. Patel ◽  
Harshad M. Damasiya ◽  
Pankaj Kapupara ◽  
Kalpesh C. Ashara
Keyword(s):  
Chemical Interaction ◽  
Poloxamer 407 ◽  
Compatibility Study ◽  
Scanning Calorimetry ◽  
Vaginal Tissue ◽  
Level Of Evidence ◽  
Vaginal Gel

Abstract Background: The in-situ gel-forming polymeric formulations offer sustained and prolonged action in comparison to conventional drug delivery systems. Aim: To formulate and evaluate in situ vaginal gel of clotrimazole. Materials and methods: Poloxamer 407 (20%) was slowly added to freezing water (5°C) with constant stirring. The prepared dispersion was refrigerated for 5 h, the different concentrations of polymers were added for preliminary batches. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were performed for clotrimazole-excipients compatibility study. The final batch was prepared and evaluated for physicochemical parameters, in vitro clotrimazole release, in vitro antifungal activity, and in vivo vaginal tissue irritation test. Results: The compatibility study showed no chemical interaction between clotrimazole and excipients used. The evaluation parameters showed that clotrimazole release was in the range of 8 to 10 h, gelling temperature was in the range of 27–35°C, gelling time was in the range of 28–34 sec, pH was in the range of 4.4–4.8, and viscosities were in the range of 16.4–182.6 cP (solution form) and 10,500–20,756 cP (gel form). The zone of inhibitions for clotrimazole pure drug, the marketed vaginal gel of clotrimazole, and optimized gel formulation was 9.15±0.75 mm, 14.35±1.12 mm, and 18.85±1.56 mm, respectively (p < 0.0001, q = 5.98). An optimized gel formulation was not irritant to vaginal tissue. Conclusion: It was possible to formulate effective in situ vaginal gel for control release action of clotrimazole. Level of Evidence: IIC.

scholarly journals OPHTHALMIC IN-SITU SUSTAINED GEL OF CIPROFLOXACIN, PREPARATION AND EVALUATION STUDY

2018 ◽  
Vol 10 (4) ◽  
pp. 153 ◽  
Author(s):  
Fadia Yassir Al-bazzaz ◽  
Myasar Al-kotaji
Keyword(s):  
Hydroxypropyl Methylcellulose ◽  
In Vitro Release ◽  
Poloxamer 407 ◽  
Gelling Agent ◽  
In Situ Gel ◽  
Viscosity Modifier ◽  
Vitro Release

Objective: This work aims to formulate and evaluate an ophthalmic in-situ gel of ciprofloxacin hydrochloride (HCl) using poloxamer 407 (P407) as a gelling agent and hydroxypropyl methylcellulose (HPMC) as a viscosity modifier. The objective of this work was to prolong the contact time as the in-situ gel will be converted into a gel upon contact with the cul-de-sac. Methods: Ciprofloxacin HCl ophthalmic in-situ gel was prepared by utilizing (P407) as a temperature-dependent polymer while hydroxypropyl methylcellulose was used as a viscosity modifier. The system was evaluated for physical appearance, pH, drug content, sterility, irritancy and stability. In addition, gelation temperature and a viscosity at different shear rates and different temperatures were studied. The compatibility of the polymer with ciprofloxacin was studied by using fourier transform infrared spectroscopy (FTIR). The in vitro release of the drug was also evaluated and supported by a preliminary in vivo test.Results: The results showed that the prepared formulas were clear, with acceptable pH and the drug contents were within the acceptable limits. FTIR results detected no incompatibility between poloxamer 407 and ciprofloxacin HCl. Notably, the viscosity of the system showed a pseudoplastic behaviour where a reduction in viscosity upon increasing the shear rate was observed. The in vitro release study confirmed the prolongation of the release of the optimized formula (F6) up to 8 h. Upon application of F6 into eyes of rabbits there was no irritancy. In addition, in vivo elimination study showed a prolonged contact for the in-situ gel in comparison with the rapid clearance of eye drop. Stability study indicated the stability of the optimized formula (F6). Conclusion: The prepared optimized formula (F6) represents a successful, safe, stable and prolonged release in-situ gel formula of ciprofloxacin.

scholarly journals DEVELOPMENT OF FROVATRIPTAN SUCCINATE MICROEMULSION FOR NASAL DELIVERY: OPTIMIZATION, IN VITRO AND IN VIVO EVALUATION

2019 ◽  
pp. 292-300 ◽  
Author(s):  
UPENDRA C GALGATTE ◽  
PRAVIN D CHAUDHARI
Keyword(s):  
Nasal Mucosa ◽  
Structural Changes ◽  
Research Work ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Pharmacokinetic Parameters ◽  
Albino Rats ◽  
In Vitro Tests ◽  
Lattice Design

Objective: The main objective of the present research work was to develop, optimize, and characterize microemulsion (ME) of frovatriptan succinate to improve brain transport. Methods: The pseudoternary phase diagrams were constructed for ME formulations composed of Capmul MCM, Cremophor EL, and propylene glycol. Frovatriptan succinate-loaded ME was optimized by simplex lattice design having the concentration of oil, surfactant, and cosurfactant representing three apex points on the triangle. These were taken as independent variables and percentage drug release as a response variable. All developed batches of ME were characterized for in vitro tests, histopathology study, and pharmacokinetics in Swiss albino rats. Results: Clear MEs were obtained. F5 having particle size – 142.0 nm, zeta potential – 17.7–−7.8 mv, refractive index – 1.38±0.20, drug content – 98.24±0.20%, and drug diffused through dialysis membrane – 85% was the optimized batch. Drug permeation through the nasal mucosa of F5 in the ex vivo study was found to be 82.32%. Histopathology microscopic study has shown that F5 does not cause any irritation and structural changes in sheep nasal mucosa. The pharmacokinetic parameters were determined after nasal and oral administration of F5. For brain tissue, after nasal administration were Cmax181±1.51 ng/ml, Tmax – 2±1.01, area under curve (AUC)0−6 – 390.0±2.08 ng.h/ml. The AUC0−6 attained by nasal ME was 3.29 times greater than oral solution. Drug targeting index of frovatriptan succinate was 2.06. This was found satisfactory. Conclusion: Microemulsion of said composition was found to be enhancing delivery of frovatriptan succinate to brain tissues through nasal route.

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 FORMULATION, DEVELOPMENT AND IN-VITRO EVALUATION OF A BAMBUTEROL HYDROCHLORIDE IN-SITU GELLING SYSTEM FOR NASAL DELIVERY

2021 ◽  
Vol 11 (6) ◽  
pp. 5-8
Author(s):  
Vipulata P. Galankar
Keyword(s):  
Gel Strength ◽  
Nasal Delivery ◽  
Nasal Administration ◽  
Formulation Development ◽  
Rotational Viscometer ◽  
In Vitro Evaluation ◽  
In Situ Nasal Gel ◽  
In Situ Gelling

The goal of this project was to design, develop, and in-vitro evaluation of an in-situ gelling system for nasal administration of Bambuterol hydrochloride. All of the batches were prepared using different concentration of pectin, given different doses of simulated nasal electrolyte solution (SNES) i.e., 0.1 ml to 2.0 ml. All batches and formulation batches with a composition of 0.8 percent low methoxyl pectin underwent an in vitro gelation testing. The pH of the formulation reduced as the pectin content increased due to the acidic nature of pectin. The drug concentration was greater than 95%, and the apparent viscosity of the sol and gel was measured using a Brookfield viscometer (Rotational Viscometer Model). When the concentration of gelling polymer was increased from 0.5 to 1.0 percent, the gel strength (SOL) increased from 0.6 to 1 sec. The gel strength (GEL) increased from 0.7 to 13 seconds as a result of gelation. In vitro drug release experiments showed that the resulting formulations could release the medication for up to 10 hours when Higuchi kinetics were applied to all of them. The gels were stable across the six-month test period, according to the accelerated stability studies. There was no drug-polymer interaction, according to DSC and XRD analyses. Based on these findings, in situ nasal gel could be a possible drug delivery strategy for bambuterol hydrochloride, allowing it to bypass first-pass metabolism and hence improve bioavailability.

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