Formulation and Pharmacokinetic Evaluation of Ritonavir Floating Tablets in the Management of AIDS

In the current study, gastro-retentive tablets of Ritonavir was developed to increase its oral bioavailability using hydrophilic polymers HPMC K 4M, K 15M, and K 100M as release retarding agents. Polyox WSR 303 was chosen as resin, sodium bicarbonate was used as effervescent agents. The tablets were prepared by direct compression method and FTIR studies revealed that there is no interaction between the drug and polymers used for the formulation. Among all the formulations F21 containing HPMC K 100M, Crospovidone, Polyox WSR 303 and sodium bicarbonate, as gas generating agent was choosen as optimized formulation based on the evaluation parameters, floating lag time (33 sec) and total floating time (>24 h) and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product was shown 98.67% and 95.09 ± 5.01% of drug release respectively. From in vivo bioavailability studies, after oral administration of floating tablet containing 100 mg Ritonavir, the Cmax, Tmax, and AUC0–∞ of optimized gastroretentive formulation were found to be 30.11 ± 1.16μg/mL, 8.00±1.23 h and 173 ± 26.34μg*h/ml, respectively. Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for improved bioavailability.

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DEVELOPMENT AND IN VITRO–IN VIVO EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF AN ANTIRETROVIRAL AGENT RITONAVIR

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i2.29196 ◽

2019 ◽

pp. 436-443

Author(s):

SHIREESH KIRAN R ◽

CHANDRA SHEKAR B ◽

NAGENDRA BABU B

Keyword(s):

Drug Release ◽

Residence Time ◽

Extended Release ◽

In Vitro Dissolution ◽

Floating Tablets ◽

Gastric Residence Time ◽

Dissolution Studies ◽

Evaluation Parameters

Objective: The present research work concerns the development of the extended release of Ritonavir floating matrix tablets, designed to prolong the gastric residence time, increase the drug bioavailability, and diminish the side effects of irritating drugs. Methods: The floating tablets of Ritonavir were prepared by direct compression method using different grades of hydroxypropyl methylcellulose (HPMC), crospovidone, Polyox WSR 303, and sodium bicarbonate, as gas generating agent. Evaluation parameters and in vivo radiographic studies were conducted in suitable model. Results: Among all formulations, F21 was chosen as optimized formulation based on evaluation parameters such as floating lag time (33 s), total floating time (>24 h), and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product were shown 98.67% and 91.46±5.02% of drug release, respectively. The main appliance of medication discharge follows zero-order kinetics and non- Fickian transport by coupled diffusion and erosion. In vivo experiments maintained the potentials in extending the gastric residence time in the fasted state in beagle dogs. The mean gastric residence time of the optimized formulation found to be 330 min±40 in the stomach, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for enhanced bioavailability. Conclusion: From in vitro and in vivo radiographic studies, Ritonavir floating tablets estimated to provide novel choice for harmless, inexpensive, and extended release for the effective management of AIDS.

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DEVELOPMENT AND EVALUATION OF FLOATING TABLET OF METOPROLOL SUCCINATE FOR INCREASED BIOAVAILABILITY VIA IN VIVO STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.25979 ◽

2018 ◽

Vol 11 (8) ◽

pp. 79

Author(s):

Kauser Fatema ◽

Sadhana Shahi

Keyword(s):

Drug Release ◽

In Vivo Studies ◽

In Vitro Dissolution ◽

Physical Parameters ◽

Metoprolol Succinate ◽

Sustained Release Formulation ◽

Dissolution Study ◽

Floating Tablet

Objective: This study was performed to formulate a floating tablet using hydrophobic glyceryl behenate (GB) and hydrophilic hydroxypropyl methylcellulose polymers, optimization of the same for retention in stomach and sustained drug delivery over a period of 20 h from upper gastrointestinal tract so as to increase its oral bioavailability.Methods: Granules of GB with the metoprolol succinate (MS) was formulated and compressed with the other ingredients to formulate a floating tablet. Physiochemical parameters of an optimized formulation along with its in vitro buoyancy study, dissolution study, in vivo studies in rabbit, and stability studies were performed.Results: Differential scanning calorimetry data show no interaction between polymers and the drug MS. A 32 factorial design was applied for optimization purpose, and from ANOVA and surface response plot the best formulation (F3) was obtained. In vitro dissolution study shows sustained drug release for 20 h for all the formulations and in vivo studies using rabbit model show increased bioavailability of an optimized formulation F3 as compared to the marketed sustained release formulation of MS (25 mg). Stability study shows no comparable differences in physical parameters and the drug release of initial formulation and the one which is kept for accelerated stability testing.Conclusion: Hence, we can conclude that a floating tablet containing a combination of hydrophilic and hydrophobic polymers can be used for gastric retention for more than 20 h which will increase the oral bioavailability of MS.

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Development of Multiple-Unit Floating Drug Delivery System of Clarithromycin: Formulation, in vitro Dissolution by Modified Dissolution Apparatus, in vivo Radiographic Studies in Human Volunteers

Drug Research ◽

10.1055/s-0043-102952 ◽

2017 ◽

Vol 67 (07) ◽

pp. 412-418 ◽

Cited By ~ 2

Author(s):

Arun Reddy ◽

Narendar Reddy

Keyword(s):

Drug Release ◽

Residence Time ◽

Release Kinetics ◽

In Vitro Dissolution ◽

Physical Parameters ◽

Gastric Residence Time ◽

Human Volunteers ◽

Multiple Unit

AbstractClarithromycin (CM), a broad spectrum macrolide antibiotic used to eradicate H. pylori in peptic ulcer. Clarithromycin (CM) is well absorbed from the gastrointestinal tract, but has a bioavailability of 50% due to rapid biodegradation. The aim of this investigation was to increase the gastric residence time, and to control the drug release of clarithromycin by formulating into multiple unit floating mini-tablets. Floating tablets were prepared by using direct compression method with HPMC K4M and Polyox WSR 1105 as release retarded polymers and sodium bicarbonate as gas generating agent. The prepared mini-tablets were evaluated for thickness, weight variation, friability, hardness, drug content, in vitro buoyancy, swelling studies, in vitro dissolution studies by using modified Rossett-Rice test and in vivo radiographic studies in healthy human volunteers in fasting conditions. DSC analysis revealed that no interaction between drug and excipients. All the physical parameters of the tablets were within the acceptable limits. The optimized formulation (F6) had showed controlled drug release of 99.16±3.22% in 12 h, by zero-order release kinetics, along with floating lag time of 9.5±1.28 s and total floating time of 12±0.14 h. X-ray imaging studies revealed that in vivo gastric residence time of clarithromycin floating mini-tablet in the stomach was about 3.5 h. The results demonstrated that the developed floating mini-tablets of clarithromycin caused significant enhancement in gastric retention time along with sustained effect and increased oral bioavailability.

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Development and In Vitro – In Vivo Evaluation of Gastro-retentive Floating Tablets Containing Repaglinide

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.2.4 ◽

2018 ◽

Vol 11 (2) ◽

pp. 4026-4036

Author(s):

Poornima P ◽

Abbulu K ◽

Mukkanti K

Keyword(s):

Drug Release ◽

Residence Time ◽

Chemical Properties ◽

Matrix Tablets ◽

In Vitro Dissolution ◽

Drug Bioavailability ◽

In Vivo Evaluation ◽

Gastric Residence Time

The present investigation concerns the development of the repaglinide floating matrix tablets, which after oral administration are designed to prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. FTIR studies revealed that there is no interaction between the drug and polymers used for the formulation. Among all the formulations F21 containing HPMC K1500 PH PRM, Polyox WSR-303 and Sodium bicarbonate, as gas generating agent was selected as optimized formulation based on physico chemical properties, floating lag time (36 sec) and total floating time (>24 h). From in vitro dissolution studies, the optimized formulation F21 showed drug release of 98.92±5.19% within 24h whereas 95.09±5.01% of the drug was released from the marketed product within 1h. The major mechanism of drug release follows zero order kinetics and non-Fickian transport by coupled diffusion and erosion. In vivo experiments supported the expectations in prolonging the gastric residence time in the fasted state in beagle dogs. The mean gastric residence time for the tested tablets was 270 min±60. This result is encouraging, because a longer gastric residence time is an important condition for higher bioavailability of the drugs included in the prolonged or controlled release dosage forms.

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ALGINATE BASED GASTRO-RETENTIVE RAFT FORMING TABLETS FOR ENHANCED BIOAVAILABILITY OF TINIDAZOLE

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017v9i1.15757 ◽

2016 ◽

Vol 9 (1) ◽

pp. 16

Author(s):

Sreejan Manna ◽

Kanchi Jayasri ◽

Kancherla Radha Annapurna ◽

Lakshmi Kanta Kanthal

Keyword(s):

Drug Release ◽

Solid Dispersion ◽

Hydroxypropyl Methylcellulose ◽

Aqueous Solubility ◽

Lag Time ◽

In Vitro Dissolution ◽

Major Barrier ◽

Gastric Residence Time ◽

Gastro Retentive

Objective: Tinidazole, a nitroimidazole derivative is having low aqueous solubility which is a major barrier for systemic drug absorption. The aim of the present research was to develop gastro retentive raft forming tablets of tinidazole to achieve prolonged gastric residence time and thus higher bioavailability.Methods: Solid dispersion of tinidazole was prepared by kneading method by using methanol and polyvinylpyrrolidone (PVP). Different concentration of sodium alginate and hydroxypropyl methylcellulose (HPMC) was used to formulate a suitable raft forming tablets and then evaluated for drug content, floating lag time, raft strength, raft volume, raft weight, drug release and release kinetics.Results: Fourier transform infra-red (FT-IR) study confirms compatibility between drug and polymer. The floating lag time was found in the range of 40±4 to 60±5 s for all the formulation. Raft strength for all the formulations was within the range from 3.03±0.12 to 5.92±0.06 g. The raft volume for all the formulation was found within the range of 7.37±1.86 to 9.84±2.76 ml. Raft weight was measured after completion of raft formation for each formulation and was found in the range of 5.21±1.17 to 7.88±1.95 g. In vitro dissolution was carried up to 8 h and percentage of drug release was found to vary between 79.71±2.18 to 94.32±1.79 %.Conclusion: It can be concluded that the combination of solid dispersion and raft formation increases the bioavailability of tinidazole in tablet formulation.

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Preparation and Evaluation of Gemifloxacin Mesylate Floating Matrix Tablets in Healthy Human Volunteers

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2017.10.1.8 ◽

2017 ◽

Vol 10 (1) ◽

pp. 3623-3630

Author(s):

Bhikshapathi D. V. R. N. ◽

Haarika B ◽

Jyothi Sri S ◽

K Abbulu

Keyword(s):

Drug Release ◽

Sodium Bicarbonate ◽

Polymer Concentration ◽

Hydroxypropyl Methylcellulose ◽

Matrix Tablets ◽

Physical Parameters ◽

Drug Bioavailability ◽

Floating Tablets

The purpose of present investigation was to develop floating matrix tablets of gemifloxacin mesylate, which after oral administration could prolong the gastric residence time, increase the drug bioavailability and diminish the side effects of irritating drugs. Tablets containing drug, various viscosity grades of hydroxypropyl methylcellulose such as HPMC K4M and HPMC K15M as matrix forming agent, Sodium bicarbonate as gas-forming agent and different additives were tested for their usefulness in formulating gastric floating tablets by direct compression method. The physical parameters, in vitro buoyancy, release characteristics and in vivo radiographic study were investigated in this study. The gemifloxacin mesylate floating tablets were prepared using HPMC K4M polymer giving more sustained drug release than the tablet containing HPMC K15M. All these formulations showed floating lag time of 30 to 47 sec and total floating time more than 12 h. The drug release was decreased when polymer concentration increases and gas generating agent decreases. Formulation that contains maximum concen-tration of both HPMC K15M and sodium bicarbonate (F9) showing sufficiently sustained with 99.2% of drug release at 12 h. The drug release from optimized formulation follows Higuchi model that indicates the diffusion controlled release. The best formulation (F9) was selected based on in vitro characteristics and used in vivo radiographic studies by incorporating barium sulphate as a radio-opaque agent and the tablet remained in the stomach for about 6 h.

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An In Vivo Predictive Dissolution Methodology (iPD Methodology) with a BCS Class IIb Drug Can Predict the In Vivo Bioequivalence Results: Etoricoxib Products

Pharmaceutics ◽

10.3390/pharmaceutics13040507 ◽

2021 ◽

Vol 13 (4) ◽

pp. 507

Author(s):

Isabel Gonzalez-Alvarez ◽

Marival Bermejo ◽

Yasuhiro Tsume ◽

Alejandro Ruiz-Picazo ◽

Marta Gonzalez-Alvarez ◽

...

Keyword(s):

Plasma Concentrations ◽

In Vitro Dissolution ◽

Case Examples ◽

Dissolution Studies ◽

Weak Bases ◽

Transit Times ◽

Class Iib ◽

The Impact

The purpose of this study was to predict in vivo performance of three oral products of Etoricoxib (Arcoxia® as reference and two generic formulations in development) by conducting in vivo predictive dissolution with GIS (Gastro Intestinal Simulator) and computational analysis. Those predictions were compared with the results from previous bioequivalence (BE) human studies. Product dissolution studies were performed using a computer-controlled multicompartmental dissolution device (GIS) equipped with three dissolution chambers, representing stomach, duodenum, and jejunum, with integrated transit times and secretion rates. The measured dissolved amounts were modelled in each compartment with a set of differential equations representing transit, dissolution, and precipitation processes. The observed drug concentration by in vitro dissolution studies were directly convoluted with permeability and disposition parameters from literature to generate the predicted plasma concentrations. The GIS was able to detect the dissolution differences among reference and generic formulations in the gastric chamber where the drug solubility is high (pH 2) while the USP 2 standard dissolution test at pH 2 did not show any difference. Therefore, the current study confirms the importance of multicompartmental dissolution testing for weak bases as observed for other case examples but also the impact of excipients on duodenal and jejunal in vivo behavior.

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Organic-Inorganic Hybrid Hollow Mesoporous Organosilica Nanoparticles for Efficient Ultrasound-Based Imaging and Controlled Drug Release

Journal of Nanomaterials ◽

10.1155/2014/972475 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 18

Author(s):

Xiaoqin Qian ◽

Wenping Wang ◽

Wentao Kong ◽

Yu Chen

Keyword(s):

Drug Release ◽

Ultrasound Irradiation ◽

Controlled Drug Release ◽

Inorganic Hybrid ◽

Templating Method ◽

Anticancer Drug Delivery ◽

Cavitation Effect ◽

Contrast Enhanced

A novel anticancer drug delivery system with contrast-enhanced ultrasound-imaging performance was synthesized by a typical hard-templating method using monodispersed silica nanoparticles as the templates, which was based on unique molecularly organic/inorganic hybrid hollow periodic mesoporous organosilicas (HPMOs). The highly dispersed HPMOs show the uniform spherical morphology, large hollow interior, and well-defined mesoporous structures, which are very beneficial for ultrasound-based theranostics. The obtained HPMOs exhibit excellent performances in contrast-enhanced ultrasonography bothin vitroandin vivoand can be used for the real-time determination of the progress of lesion tissues during the chemotherapeutic process. Importantly, hydrophobic paclitaxel- (PTX-) loaded HPMOs combined with ultrasound irradiation show fast ultrasound responsiveness for controlled drug release and higherin vitroandin vivotumor inhibition rates compared with free PTX and PTX-loaded HPMOs, which is due to the enhanced ultrasound-triggered drug release and ultrasound-induced cavitation effect. Therefore, the achieved novel HPMOs-based nanoparticle systems will find broad application potentials in clinically ultrasound-based imaging and auxiliary tumor chemotherapy.

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Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride

Acta Pharmaceutica ◽

10.2478/v10007-011-0015-5 ◽

2011 ◽

Vol 61 (2) ◽

pp. 217-226 ◽

Cited By ~ 7

Author(s):

Komuravelly Someshwar ◽

Kalyani Chithaluru ◽

Tadikonda Ramarao ◽

K. Kumar

Keyword(s):

Drug Release ◽

Residence Time ◽

Release Kinetics ◽

Hydroxypropyl Methylcellulose ◽

Matrix Tablets ◽

Physical Parameters ◽

Floating Tablets ◽

Gastric Residence Time

Formulation and evaluation of effervescent floating tablets of tizanidine hydrochloride Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.

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