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 and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

scholarly journals DESIGN AND IN VITRO/IN VIVO EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF NATEGLINIDE

2018 ◽  
Vol 7 (6) ◽  
Author(s):  
Mohini Sihare ◽  
Rajendra Chouksey
Keyword(s):  
Drug Release ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Release Profile ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Release Mechanism ◽  
In Vivo Evaluation

Aim: Nateglinide is a quick acting anti-diabetic medication whose potent activity lasts for a short duration. One of the dangerous side effects of nateglinide administration is rapid hypoglycemia, a condition that needs to be monitored carefully to prevent unnecessary fatalities. The aim of the study was to develop a longer lasting and slower releasing formulation of nateglinide that could be administered just once daily. Methods: Matrix tablets of nateglinide were prepared in combination with the polymers hydroxypropylmethylcellulose (HPMC), eudragits, ethyl cellulose and polyethylene oxide and the formulated drug release patterns were evaluated using in vitro and in vivo studies. Conclusion: Of the seventeen formulated matrix tablets tested, only one formulation labelled HA-2 that contained 15% HPMC K4M demonstrated release profile we had aimed for. Further, swelling studies and scanning electron microscopic analysis confirmed the drug release mechanism of HA-2. The optimized formulation HA-2 was found to be stable at accelerated storage conditions for 3 months with respect to drug content and physical appearance. Mathematical analysis of the release kinetics of HA-2 indicated a coupling of diffusion and erosion mechanisms. In-vitro release studies and pharmacokinetic in vivo studies of HA-2 in rabbits confirmed the sustained drug release profile we had aimed for. Keywords: Hydroxypropylmethylcellulose, Matrix tablets, Nateglinide, Sustained release

scholarly journals Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Rajni Bala ◽  
Sushil Khanna ◽  
Pravin Pawar
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Content Uniformity ◽  
In Vivo Evaluation ◽  
Disintegration Time ◽  
Significant Difference ◽  
Film Formulation ◽  
Test Film

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of Cmax (95.87%), tmax (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles.

scholarly journals Preparation and preclinical evaluation of aceclofenac loaded pectinate mucoadhesive microspheres

2012 ◽  
Vol 2 (1) ◽  
pp. 8 ◽  
Author(s):  
Santanu Chakraborty ◽  
Priyanka Nayak ◽  
Bala Murali Krishna ◽  
Madhusmruti Khandai ◽  
Ashoke Kumar Ghosh
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Polymer Concentration ◽  
Research Work ◽  
In Vivo Studies ◽  
Systemic Absorption ◽  
Cross Linking ◽  
Significant Difference

The aim of the present research work was to fabricate aceclofenac loaded pectinate microspheres by ionic gelation method and evaluate the effect of different cross-linking agents and polymer concentration on particle size, encapsulation efficacy and drug release behavior. It was also investigated that whether this pectinate dosage form was able to target the drug release in intestinal region and prevent the different side effect associated with the drug in stomach or not. It was observed that particle size, encapsulation efficacy and in vitro drug release were largely depended on polymer concentration and cross-linking agents. It was also observed that pectinate microspheres showed excellent pH depended mucoadhesive properties and they were able to restrict the drug release in stomach. <em>In vitro</em> drug release study showed that alminium-pectinate microspheres have more sustaining property as compared to barium-pectinate microspheres. Holm-Sidak multiple comparison analysis suggested a significant difference in measured t<sub>50%</sub> values among all the formulations with same cross-linking agent. In vivo studies revealed that the anti inflammatory and analgesic effects induced by pectinate microspheres were significantly high and prolonged as compared to pure drug. So, pectinate microspheres can be an excellent carrier for targeting the delivery of aceclofenac as well as help in improving the patient compliance by prolonging the systemic absorption.

scholarly journals Formulation and Evaluation of Fast Dissolving Film of Losartan Potassium

2021 ◽  
Vol 68 (1) ◽  
Author(s):  
Bhageerathy A ◽  
Sandhya Murali ◽  
eny Sara Thomas ◽  
Sigi Vasanthkumar ◽  
Prasanth V V
Keyword(s):  
Drug Release ◽  
Physical Stability ◽  
Losartan Potassium ◽  
In Vivo Studies ◽  
Disintegration Time ◽  
Drug Content ◽  
Weight Variation ◽  
Significant Difference

A total of nine formulations of fast dissolving films of Losartan Potassium were developed by solvent casting method using film forming polymers such as HPMC E5, E15 and E50 and other film modifiers. The appearances of films were transparent, thin, flexible, elastic, smooth and transparent. The weight variation ranged between 16.14 ± 0.192 and 17.31 ± 0.313 and showed that there was no significant difference in the weight of individual formulations. All the formulations showed more than 150 of folding endurance. The drug content was found to be in an acceptable range for all the formulations which indicated uniform distribution of drug. A rapid dissolution of all the film was observed by the dissolution test, in which above 90% of Losartan Potassium was released within 5 min. The formulation F1 showed maximum drug release (98.73) within 5 minutes. Based on the in vitro drug release, drug content and in vitro disintegration time it is found that F1 was selected as the best formulation. The formulations showed satisfactory physical stability at 40°C at 75 % RH. Losartan Potassium (LOSAR-25) is shown in Figure 4. From the results of comparative studies of marketed product and it found that F1 showed 98.73% release within 5 min and LOSAR 25 showed 90.76% release in 30 min. In vitro studies indicate that this potential drug delivery system has considerably good stability and release profile. Nevertheless, further in vivo studies are warranted to confirm these results.

Design and in vivo Evaluation of Gastro-retentive Floating Capsules of Amlodipine Besylate in Healthy Human Volunteers

2017 ◽  
Vol 10 (6) ◽  
pp. 3891-3899
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Chenna Madipalli Shalina ◽  
Vishnu Pulavarthy ◽  
Viswaja Medipally
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Sustained Release ◽  
In Vivo Studies ◽  
Amlodipine Besylate ◽  
In Vivo Evaluation ◽  
Healthy Human ◽  
Gastro Retentive

The aim of this study was to explore the application of Gelucire 43/01 for the design of sustained release gastro retentive drug delivery system of Amlodipine besylate. Gelucire 43/01 has been used in floating sustained release formulations to prolong gastric residence time and increase its bioavailability. Gelucire 43/01 in combination with HPMC and Polyox was used as a release retarding polymer. HPMC of various viscosity grades HPMC K4M, HPMC K15M and HPMC K100M in combination of Gelucire were tested to obtain optimal total floating time as well as controlled drug release for prolonged period. Melt granulation technique has been used to prepare gastro retentive Amlodipine besylate formulations. All the formulations were evaluated in vitro for their floating ability and drug release. The floating times of all tablet formulations were greater than 12h. HPMC K4M in combination with Gelucire as polymeric matrix enhanced the drug release due to addition of hydrophilic polymer facilitated the swelling and erosion of the tablets. Incorporation of low viscosity polymer HPMC K100 M resulted in optimal floating as well as drug release for longer time. In vivo studies of optimized formulation show floating ability for 6 h in stomach. The results indicate that Gelucire 43/01 in combination with dissolution enhancers HPMC increase the permeability of the wax matrix, which provides improved dissolution thereby bioavailability of Amlodipine besylate and can be considered as a carrier for the development of sustained release floating drug delivery systems.  

In vitro and In vivo Evaluation of Propranolol Microspheres Loaded Buccal Gel

2017 ◽  
Vol 10 (2) ◽  
pp. 3661-3668
Author(s):  
Gajanan J Deshmukh ◽  
M. Mohan Varma ◽  
Bhikshapathi D. V. R. N.
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Ex Vivo ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
In Vivo Evaluation ◽  
Mechanical Stirring ◽  
Zero Order Kinetics

The selected propranolol microsphere formulation, S6 was employed for gel formulation with a variety of polymers like Carbopol 934, HPMC and Sodium CMC by mechanical stirring method in order to develop a sustained release propranolol microspheres containing bioadhesive gel. The prepared bioadhesive gels were evaluated for pH, viscosity, %drug content, in vitro drug release studies, bioadhesion, ex vivo permeation studies, accelerated stability and in vivo bioavailability studies. From all the above studies FG3 was found to be optimized formulation. In vitro experiments indicated a sustained release of 98.92% over 12 h and an acceptable bioadhesion quality for formulation FG3. Optimized formulation was characterized for FTIR, SEM and stability studies and found to be stable. Propranolol Optimized formulation exhibited significant increased bioavailability in vivo when compared with marketed tablet. The drug release from the optimized formulation follows zero order kinetics with anomalous Non-fickian diffusion. In vivo studies revealed that Propranolol Optimized formulation FG3 exhibited significant increased bioavailability when compared with marketed product, due to reduced first pass metabolism, when it is administered by the buccal route. Hence, it can be concluded that the formulation FG3 has potential to deliver Propranolol in a controlled and constant manner for prolong period over other formulations and can be adopted for a successful delivery of propranolol for buccal use.

FORMULATION AND EVALUATION OF MICROSPHERES FOR NASAL DELIVERY OF ANTI-HYPERTENSIVE DRUG

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (10) ◽  
pp. 21-26
Author(s):  
S. S Shelake ◽  
◽  
R. M Mhetre ◽  
S. V Patil ◽  
S. S Patil ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Nasal Delivery ◽  
In Vivo Studies ◽  
Oral Drug ◽  
Hypertensive Drug

Lisinopril is used in the treatment of hypertension and heart failure in myocardial infarction and also in diabetic nephropathy. It is very poorly absorbed from GIT. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The microspheres prepared by emulsion solvent evaporation method were characterized for encapsulation efficiency, drug loading, particle size, surface morphology, degree of swelling, ex vivo mucoadhesion, drug release and ex vivo diffusion studies. Entrapment efficiency of microspheres was in range of 84.95±0.50% to 97.44±0.61% mucoadhesion was 83.76% and 94.41% and drug release up to 40 minutes was 53.66% to 88.32%. In ex vivo studies, the microspheres showed good bioavailability by nasal route compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol-based formulation for the delivery of lisinopril.

scholarly journals IN VIVO EVALUATION OF QUINAPRIL TRILAYERED MATRIX TABLETS

2021 ◽  
pp. 117-125
Author(s):  
ASHWIN K ◽  
RAMA MOHAN REDDY T
Keyword(s):  
Drug Release ◽  
Drug Concentration ◽  
In Vitro Release ◽  
Matrix Tablets ◽  
In Vivo Studies ◽  
Matrix Tablet ◽  
In Vivo Evaluation ◽  
Drug Content

Objective: The aim was to design, formulate, and evaluate the trilayer matrix tablets incorporated with quinapril for extend drug release. Methods: Quinapril trilayer matrix tablets were formulated using design of experiment software wherein initially 27 formulations (QF1-QF27) were designed for active layer from which one best formulation was chosen based on drug content, swelling index and in vitro release studies. The chosen formulation was formulated into extended release trilayed matrix tablet by varying proportions of polymers by direct compression and was evaluated for various physicochemical parameters, drug release. Best formulation was characterized for Fourier transform infrared (FTIR), stability, and pharmacokinetic study. Results: Out of 27 formulations highest drug release was exhibited by QF16 (98.85%) which was formulated into trilayer matrix tablets (AQF16- HQF16). Out of which EQF16 was found to exhibit highest values with 98.42% swelling index, 99.56% drug content, and 99.72% drug release in 24 h. All quinapril trilayer formulations showed zero-order and first-order for marketed product. The optimized formulation EQF16 was found to exhibit no interaction with excipients interpreted by FTIR and no significant changes were observed after loading for stability. In vivo studies conducted using optimized formulation EQF16 attained peak drug concentration (Tmax) of 4.0±0.06 and 1.0±0.03 h for the optimized and commercial formulations, respectively, while mean maximum drug concentration (Cmax) was 302.64±0.07 ng/mL and was significant (p<0.05) as compared to the quinapril marketed product formulation 358.78±0.75 ng/mL. Conclusion: Hence, quinapril was successfully formulated into trilayer matrix tablet and found to be stable.

scholarly journals DEVELOPMENT AND IN VIVO EVALUATION OF MUCOADHESIVE MICROSPHERES USING PIRENZEPINE

2018 ◽  
Vol 11 (7) ◽  
pp. 296
Author(s):  
Kanteepan P ◽  
Bhikshapathi Dvrn
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Extended Period ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
Technique Evaluation ◽  
Evaluation Parameters

Objective: The current investigation objective was to fabricate gastroretentive mucoadhesive microspheres of pirenzepine and to investigate the pharmacokinetic parameters of optimized formulation in comparison with a marketed product.Methods: Pirenzepine mucoadhesive microspheres prepared using ionotropic gelation technique. Evaluation parameters and characterization such as Fourier transform infrared (FTIR) and scanning electron microscopy were performed. In vivo bioavailability studies were conducted in rabbits. The technique used was found to be handling easy, inexpensive, and reproducible process.Results: Among the total 14 formulations, M13 formulation was optimized and showed free flowing with good packability. FTIR studies investigated incompatibility were not observed between drug and excipients. The optimized formulation (M13) showed best cumulative percentage drug release of pirenzepine up to 99.07±0.17% within 12 h whereas marketed product displayed the drug release of 95.23±0.21% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer–Peppas model (R2=0.951 and 0.994), respectively. Optimized formulation (M13) was stable at 40°C±2°C/75% RH±5% RH for 6 months. Form in vivo studies, the optimized formulation bioavailability was much higher than the marketed product.Conclusion: Microspheres would be a promising drug delivery system could play a potentially significant role in pharmaceutical drug delivery in a controlled manner for an extended period of time for effective management of gastritis.

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