scholarly journals Design and Evaluation of Losartan Potassium Effervescent Floating Matrix Tablets: In Vivo X-ray Imaging and Pharmacokinetic Studies in Albino Rabbits

Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3476
Author(s):  
Mohamed Rahamathulla ◽  
Srinivasan Saisivam ◽  
Abdullah Alshetaili ◽  
Umme Hani ◽  
Hosahalli Veerabhadrappa Gangadharappa ◽  
...  
Keyword(s):  
Matrix Tablets ◽  
Losartan Potassium ◽  
Fickian Diffusion ◽  
Pharmacokinetic Studies ◽  
Matrix Tablet ◽  
X Ray ◽  
X Ray Imaging ◽  
Compression Characteristics

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug–polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit’s stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively.

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.

scholarly journals Design and Evaluation of Colon Specific Delivery of Budesonide Core in Coat Matrix Tablet Used In Local Ulcerative Colitis

2016 ◽  
Vol 8 (02) ◽  
Author(s):  
Mallikarjuna M. ◽  
Ramakrishna A.
Keyword(s):  
Ulcerative Colitis ◽  
Drug Release ◽  
Matrix Tablets ◽  
Angle Of Repose ◽  
In Vitro Dissolution ◽  
Matrix Tablet ◽  
Cecal Content ◽  
S 100

In the present investigation planned to study the less explored sterculia gum as matrix carrier of Budesonide to colon. Developed the formulations from B1 to B4 contains alone sterculia gum and its proportion increased gradually in the formulation. The formulations B5 to B10 contain the sterculia gum in combination with Eudragit S 100 and the hydrophilic, hydrophobic polymer. The budesonide core in coat matrix tablets was prepared by direct compression method. The powder bed of the formulations is evaluated for pre compressional characteristics like bulk density, tapped density, compressibility index and angle of repose. The compressed budesonide core in coat matrix tablets were evaluated for post compressional characteristics like thickness, diameter, hardness, disintegration, friability and to understand the drug release pattern and to correlate the in vivo condition, the in vitro dissolution performed in three different gastro intestinal pH at 1.2, pH 7.4 and pH 6.8 with and without 4% rat cecal content. The in vitro dissolution results of formulations ascertain that sterculia gum alone in formulation uncontrolled the drug release in first 5 hrs and carried lesser amount of drug to colon. The formulations B8 in the first 5 hours released 4.3% and carried the larger amount of drug to colon and in absence of rat cecal content released 90% and in presences of 4% rat cecal content released 99% of drug, indicating the sterculia gum undergoes enzymatic degradation and this formulation is considered as potential in targeting the budesonide to colon in the local ulcerative colitis

Abstract 5281: Bioluminescence Imaging of X-Ray Visible Microencapsulated Mesenchymal Stem Cells for Cell Based Therapy of Peripheral Arterial Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dorota A Kedziorek ◽  
Piotr Walczak ◽  
Yingli Fu ◽  
Nicole Azene ◽  
Aravind Arepally ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
X Ray ◽  
Encapsulated Cells ◽  
X Ray Imaging ◽  
Peripheral Arterial

Introduction: Therapeutic angiogenesis in Peripheral Arterial Disease (PAD) using stem cell therapy is potentially complicated by immunorejection. To overcome this problem, microen-capsulation using the alginate-poly-L-lysine (PLL)-alginate (APA) method was developed to provide a protective porous bubble to block antibodies but allow exchange of small molecules. Recently, we have developed a method to enable X-ray detection of these capsules. However, cell survival within the capsules could not be determined. Plus PLL can be mildly cytotoxic. In the present study, we combined reporter gene methods to verify cell survival with X-ray detection of the microcapsules in a rabbit PAD model and studied the PLL impact on cell viability. Methods: Rabbit mesenchymal stem cells (MSCs) were transfected with triple fusion (TF) reporter gene for bioluminescence (firefly luciferase), fluorescence (red fluorescent protein) and PET (truncated thymidine kinase). TF-MSCs were encapsulated in the perfluorooctyl bromide (PFOB) capsules to enable computed tomographic detection. Capsule crosslinking was performed with three PLL concentrations, i.e., 0.005%, 0.025% and 0.05%. Bioluminescent imaging (BLI) was used to monitor cells survival for one week in vitro and after intramuscular injection in vivo . Results: Serial in vitro BLI enabled the detection of viable encapsulated MSCs without detrimental signal degradation (~13% decrease of BLI signal intensity after PFOB encapsulation comparing to equal number of naked MSCs). PLL did not result in cell death; higher PLL concentrations were correlated with stronger BLI signal. BLI signal production was only slightly reduced by second layer of alginate (~80% for 0.05% PLL). In vivo BLI demonstrated the detection of naked, APA, and PFOB-encapsulated TF-MSCs. X-ray imaging enabled PFOB microcapsules detection relative to vasculature. Conclusion: BLI allows monitoring of encapsulated cells survival. PLL concentrations ≤ 0.05% appear safe for encapsulated cells with higher concentration being associated with enhanced crosslinking and capsule stability. MSCs expressing TF reporter in PFOB microcapsules enables dual monitoring of cell delivery/capsule tracking by X-ray imaging and cell viability with BLI.

scholarly journals DESIGN AND COMPARATIVE EVALUATION OF CLARITHROMYCIN GASTRIC BIOADHESIVE TABLETS BY EX VIVO AND IN VIVO METHODS

2018 ◽  
Vol 11 (4) ◽  
pp. 248
Author(s):  
Nishad Km ◽  
Arul B ◽  
Rajasekaran S
Keyword(s):  
Controlled Release ◽  
Imaging Technique ◽  
Ex Vivo ◽  
In Vitro Dissolution ◽  
Natural Polymers ◽  
Drug Bioavailability ◽  
X Ray ◽  
X Ray Imaging

 Objective: The present investigation was to formulate controlled release of mucoadhesive clarithromycin tablets using natural polymers.Methods: Tamarind seed polysaccharide obtained from Tamarindus indica and chitosan act as natural polymers. The formulated tablets of the combined form of thrombospondin (TSP) and chitosan were analyzed by in vitro dissolution method. The optimized formulations were selected for ex vivo and in vivo studies and compared with hydroxypropyl methylcellulose K100 polymer by evaluating gastric retention period by X-ray imaging technique, and drug bioavailability by a pharmacokinetic method from blood samples was determined by high-performance liquid chromatography-mass spectrometry method.Results: The gastric mucoadhesive tablets were prepared using chito-TSP polymers. The in vitro drug release showed good release character for 24 h. The ex vivo studies of tablets showed good adhesive property for a long time. The X-ray imaging technique also proved the adhesive character of tablets. From blood serum sample of rabbits, bioavailability of the drug is in according to the controlled release mechanism.Conclusion: The selected formulations were subjected to stability studies. The study concluded that combination of chitosan and TSP is best natural polymer for mucoadhesion by the advantages of controlled release and biodegradation.

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.

scholarly journals Formulation and Evaluation of Bilayer Matrix Tablets of Nebivolol Hydrochloride and Valsartan

2019 ◽  
Vol 9 (4-s) ◽  
pp. 82-93
Author(s):  
Selvi Arunkumar ◽  
L. Srinivas ◽  
D. Satyavati ◽  
C. Emmanuel
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Immediate Release ◽  
Matrix Tablets ◽  
Pharmacokinetic Studies ◽  
Drug Content ◽  
Bilayer Tablets ◽  
Nebivolol Hydrochloride

The present study is an attempt to develop bilayer matrix tablets of Nebivolol Hydrochloride and Valsartan with immediate release for Nebivolol Hydrochloride and sustained release for Valsartan. Superdisintegrants such as sodium starch glycolate and Crosscarmellose sodium were evaluated for immediate release of Nebivolol Hydrochloride and polymers HPMC K100M and K4M for sustained release of Valsartan. Preformulation studies were performed prior to compression. The compressed bilayer tablets were evaluated for weight variation, thickness, hardness, friability, drug content and in vitro drug release using USP dissolution apparatus type 2 in 0.01N HCl and phosphate buffer pH 6.8. All the pre and post compression parameters were found to be within the acceptable limits. The results of dissolution show that the formulations B3 was the best of all immediate and sustained release layer batches. The release kinetics of Valsartan was subject to curve fitting analysis in order to identify the best fit kinetic model. The regression analysis proves that the best formulations follow zero order release and drug release by diffusion process based on Fick’s law of diffusion. The data for stability studies infer no considerable change in drug content and dissolution rates as per ICH guidelines. The best formulation B3 was subjected to in vivo pharmacokinetic studies in rabbit model. In vitro, In vivo correlation (IVIVC) showed considerable linearity. Hence a novel bilayer tablet formulation of Nebivolol Hydrochloride and Valsartan was successfully developed by combining both immediate (IR) and sustained (SR) release layers. Keywords: Bilayer tablets, fixed unit dosage form, Nebivolol hydrochloride, Valsartan, LC-MS analysis.

scholarly journals Bimodal Ultrasound and X-Ray Bioimaging Properties of Particulate Calcium Fluoride Biomaterial

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5447
Author(s):  
Cristhian Marcelo Chingo Aimacaña ◽  
Kevin O. Pila ◽  
Dilan A. Quinchiguango Perez ◽  
Alexis Debut ◽  
Mohamed F. Attia ◽  
...  
Keyword(s):  
Photoelectron Spectroscopy ◽  
Calcium Fluoride ◽  
In Vitro Cytotoxicity ◽  
Diagnostic Methods ◽  
Face Centered Cubic ◽  
X Ray ◽  
Peak Broadening ◽  
X Ray Imaging

Ultrasound (US) and X-ray imaging are diagnostic methods that are commonly used to image internal body structures. Several organic and inorganic imaging contrast agents are commercially available. However, their synthesis and purification remain challenging, in addition to posing safety issues. Here, we report on the promise of widespread, safe, and easy-to-produce particulate calcium fluoride (part-CaF2) as a bimodal US and X-ray contrast agent. Pure and highly crystalline part-CaF2 is obtained using a cheap commercial product. Scanning electron microscopy (SEM) depicts the morphology of these particles, while energy-dispersive X-ray spectroscopy (EDS) confirms their chemical composition. Diffuse reflectance ultraviolet-visible spectroscopy highlights their insulating behavior. The X-ray diffraction (XRD) pattern reveals that part-CaF2 crystallizes in the face-centered cubic cell lattice. Further analyses regarding peak broadening are performed using the Scherrer and Williamson–Hall (W-H) methods, which pinpoint the small crystallite size and the presence of lattice strain. X-ray photoelectron spectroscopy (XPS) solely exhibits specific peaks related to CaF2, confirming the absence of any contamination. Additionally, in vitro cytotoxicity and in vivo maximum tolerated dose (MTD) tests prove the biocompatibility of part-CaF2. Finally, the results of the US and X-ray imaging tests strongly signal that part-CaF2 could be exploited in bimodal bioimaging applications. These findings may shed a new light on calcium fluoride and the opportunities it offers in biomedical engineering.

scholarly journals In Vitro - In Vivo Evaluation Of E/R Trilayer Matrix Tablets Containing Solid Dispersion Of Atorvastatin

2016 ◽  
Vol 8 (3) ◽  
pp. 107
Author(s):  
A Thirupathaiah ◽  
R Shyam Sunder
Keyword(s):  
Extended Release ◽  
Chemical Interaction ◽  
Research Work ◽  
Matrix Tablets ◽  
Drug Dissolution ◽  
Matrix Tablet ◽  
Dissolution Profile ◽  
Reference Standard

<p>Investigation of <em>in vitro/in vivo</em> behaviour of extended release tablets containing solid dispersions of Atorvastatin is the focus of the present research work. Atorvastatin trilayer matrix tablets were prepared by direct compression method and consisted of middle active layer with different grades of hydroxypropylmethylcellulose (HPMC), ethyl cellulose and Carbopol 934P. Barrier layers are prepared with hydrophobic polymers carnauba wax and xanthan gum. Based on the evaluation parameters, drug dissolution profile and release order kinetics HF16 was found to be optimized formulation. The developed drug delivery system provided prolonged drug release rates over a period of 24 h. The release profile of the optimized formulation (HF16) was described by the Zero-order and best fitted to Higuchi model. FTIR confirmed that there was no chemical interaction between drug and excipients used in the formulation. . In vivo bioavailability studies were conducted for optimized formulation HF16 and reference standard. The optimized formulation of Atorvastatin trilayer matrix tablet was shown significant plasma concentration with extended release and maintained for 24 hrs with patient compliance by reducing the dosage frequency, when compared with reference standard. </p>

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