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 FORMULATION, IN VITRO, AND IN VIVO EVALUATION OF TASTE-MASKED ORAL DISINTEGRATING TABLETS OF FEXOFENADINE HYDROCHLORIDE USING SEMISYNTHETIC AND NATURAL SUPERDISINTEGRANTS

2021 ◽  
pp. 99-108
Author(s):  
NAGADANI SWARNALATHA ◽  
VIDYAVATHI MARAVAJHALA
Keyword(s):  
Desirability Function ◽  
Research Work ◽  
In Vivo Studies ◽  
Taste Masking ◽  
Wet Granulation ◽  
Maximum Plasma ◽  
In Vivo Evaluation ◽  
Eudragit Epo

Objective: The aim of the present research work was to prepare and evaluate taste-masked oral disintegrating tablets (ODT) of Fexofenadine hydrochloride. Methods: In the present work, Eudragit EPO, a taste masking agent and Karaya gum (GK) (natural), Sodium starch glycolate, and Croscarmellose sodium (CCS) (semi-synthetic) super disintegrants in three ratios (3, 6,9%) were used. Taste masked granules were prepared by different ratios of the drug: Eudragit EPO (1:1, 1:1.5, 1:2) by wet granulation method. The optimized taste-masked granules (1:2) were selected by sensory evaluation test to prepare 9 Fexofenadine ODT (FH1-FH9) formulations. These were evaluated for different parameters. Then desirability function (DF) was calculated for all formulations using disintegration time (DT), time taken for the tablet to release 90% of the drug (t 90%), and % drug dissolved in 10 min (Q10) as significant parameters. Results: The best formulation (FH6) showed the highest DF value due to less DT and 100% in vitro drug release within 15 min. Thus, FH6 formulation containing 9% CCS was selected as the best among the prepared formulations to which in vivo studies were performed on rabbits to find maximum plasma concentration (Cmax), time taken to reach maximum concentration (tmax), area under the curve (AUC), rate of elimination (Kel), absorption rate (Ka) and half-life(t1/2) and compared with Fexofenadine (Allegra) marketed tablets. Total bioavailability was increased for the test formulation compared to the reference formulation. Conclusion: Fexofenadine was successfully prepared as ODT with increased AUC and decreased tmax to which stability studies were conducted which were found to be stable.

scholarly journals Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies

2021 ◽  
Vol 62 (2) ◽  
pp. 144-162
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Oral Administration ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula.

Quality by Design enabled anti-hypertensive Floating drug delivery system by Risk assessment and Design of Experiment (DoE) – In vitro – In vivo correlation studies

2021 ◽  
Vol 16 ◽  
Author(s):  
Mounika Chidurala ◽  
Raveendra Reddy J
Keyword(s):  
Drug Release ◽  
Risk Analysis ◽  
Quality By Design ◽  
Release Kinetics ◽  
Cost Effective ◽  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies

Background: The present research aimed to develop and optimize extended-release floating tablets of Sacubitril and Valsartan through Quality by Design (QbD) approach. Risk analysis by formulation assessment and process parameters showed that optimizing the levels of the polymer will minimize high risk to meet the target profile. A two (2) level three (3) full factorial experimental design along with midpoints was carefully chosen for optimization and statistical analysis. Based on the literature, the independent and dependent variables were selected. Results: HPMC K100, Carbopol 934P had a positive effect, whereas Ethylcellulose had a negative effect on Floating time, drug release at 2 h, drug release at 12 h and, 50% responses. Drug release kinetics followed the first-order release with Higuchi and Fickian diffusion. Contour and overlay plots were utilized for an assortment of design space and optimized formula. ANOVA results of all the factors exhibited significance at p<0.05. Abdominal X-ray imaging of the optimized tablets on healthy rabbit’s stomach confirmed the floating behavior for more than 12 h. In vivo pharmacokinetic studies in rabbits showed that the optimized formulation exhibited prolonged and extended drug release with improved Cmax, tmax, AUCo-t, and t1/2 of test product when compared to marketed product. IVIVC model was developed by using dissolution data of in vitro and pharmacokinetics data of in-vivo by de-convolution method (Wagner-Nelson method). Conclusion: The Quality by Design implementation in the formulation and optimization abridged the number of trials to produce a cost-effective formula. In vivo studies confirmed that the formula was successfully developed with extended floating time (12 h) and drug release by risk analysis and experimental designs. Level A correlation was observed which confirmed a good correlation between in vitro and in vivo data.

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.

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.  

Formulation and Evaluation of Gastro-Retentive Floating Extended Release Metoprolol Tablets using Sodium Alginate and HPMC K-100M Combination

2015 ◽  
Vol 8 (3) ◽  
pp. 2947-2954
Author(s):  
Ashok Thulluru ◽  
M. Mohan Varma ◽  
C M Setty ◽  
Pavan Kumar Chintamaneni ◽  
S. Sriharsha Vardhan
Keyword(s):  
Drug Release ◽  
Sodium Alginate ◽  
Fickian Diffusion ◽  
Wet Granulation ◽  
Average Weight ◽  
Metoprolol Succinate ◽  
Floating Tablets ◽  
Zero Order Kinetics ◽  
Gastro Retentive

The present study was aimed to convert Metoprolol Succinate convert into Gastro Retentive Floating Tablet (GRFT). The gas generating floating tablets of Metoprolol Succinate were prepared to increase the gastric retention and to extend the drug release up to 12 hr. and thereby enhancing its bioavailability. The floating tablets were formulated using HPMCK 100M alone and with the combination of sodium alginate to the polymer of varying concentrations. The tablets were prepared by non-aqueous wet granulation method. The formulated granules were evaluated for pre-compression studies, after the compression of tablets they were subjected to various post-compression studies: Average weight, thickness, density, hardness, % friability, % drug content, (In vitro buoyancy studies: floating time, total floating time and matrix integrity up to 12 hr) and the In vitro drug release studies. The optimized formulation (F4) was found to follow a near perfect zero order kinetics (regression coefficient,      r2 = 0.978). Higuchi plot for formulation, F4, showed r2 value of 0.978, suggesting that the diffusion and erosion plays an important role in the controlled release of the drug. The data was fitted to the Korsemeyer-Peppa’s equation; and the value of the diffusion component (n=0.654), for the formulation F4, indicated that the drug release follows non-Fickian diffusion.  

scholarly journals Development and evaluation of gastroretentive norfloxacin floating tablets

2009 ◽  
Vol 59 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Ramesh Bomma ◽  
Rongala Swamy Naidu ◽  
Madhusudan Yamsani ◽  
Kishan Veerabrahma
Keyword(s):  
Drug Release ◽  
Hydroxypropyl Methylcellulose ◽  
Matrix Tablets ◽  
Fickian Diffusion ◽  
Release Mechanism ◽  
Wet Granulation ◽  
Drug Bioavailability ◽  
Floating Tablets

Development and evaluation of gastroretentive norfloxacin floating tabletsFloating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxypropyl methylcellulose (HPMC K4M, HPMC K100M) and xanthan gum. Tablets were evaluated for their physical characteristics,viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied forin vitrodrug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based onin vitrocharacteristics and was usedin vivoradiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs.

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.

scholarly journals In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1753 ◽  
Author(s):  
Joanna Ziemska ◽  
Jolanta Solecka ◽  
Małgorzata Jarończyk
Keyword(s):  
Leucine Aminopeptidase ◽  
Three Dimensional ◽  
3D Qsar ◽  
In Vivo Studies ◽  
Statistical Parameters ◽  
Qsar Study ◽  
Lipinski’S Rule ◽  
Aminopeptidase Inhibitors

Cancers are the leading cause of deaths worldwide. In 2018, an estimated 18.1 million new cancer cases and 9.6 million cancer-related deaths occurred globally. Several previous studies have shown that the enzyme, leucine aminopeptidase is involved in pathological conditions such as cancer. On the basis of the knowledge that isoquinoline alkaloids have antiproliferative activity and inhibitory activity towards leucine aminopeptidase, the present study was conducted a study which involved database search, virtual screening, and design of new potential leucine aminopeptidase inhibitors with a scaffold based on 3,4-dihydroisoquinoline. These compounds were then filtered through Lipinski’s “rule of five,” and 25 081 of them were then subjected to molecular docking. Next, three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed for the selected group of compounds with the best binding score results. The developed model, calculated by leave-one-out method, showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.997) and q2 (0.717). Further, 35 compounds were identified to have an excellent predictive reliability. Finally, nine selected compounds were evaluated for drug-likeness and different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Our methodology suggested that compounds with 3,4-dihydroisoquinoline moiety were potentially active in inhibiting leucine aminopeptidase and could be used for further in-depth in vitro and in vivo studies.

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.

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