scholarly journals Muco-adhesive buccal tablets of candesartan cilexetil for oral delivery: preparation, in-vitro and ex-vivo evaluation

2021 ◽  
Vol 11 (1-s) ◽  
pp. 35-42
Author(s):  
Kumara Swamy Samanthula ◽  
Agaiah Goud Bairi ◽  
CB Mahendra Kumar
Keyword(s):  
Candesartan Cilexetil ◽  
Ex Vivo ◽  
Methyl Cellulose ◽  
Carboxy Methyl Cellulose ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Pass Metabolism ◽  
Carboxy Methyl

Candesartan cilexetil (CC) is an angiotensin II-receptor blocker (ARB). The antihypertensive effect of CC 4-16 mg/day was as great as that of other once-daily dosage regimens. Candesartan cilexetil has high first-pass metabolism and low oral bioavailability. The bioavailability of such drugs may be significantly improved if delivered through the buccal route; hence mucosal delivery is one of the alternative methods of systemic drug delivery. This study’s objective was to develop mucoadhesive buccal tablets of candesartan cilexetil using carbopol-934P, hydroxyl propyl methyl cellulose (HPMC), Eudragit RLPO, and sodium carboxy methyl cellulose (Na-CMC) as mucoadhesive polymers. Prepared CC buccal tablet formulations were evaluated for an optimized system based on physicochemical properties, ex-vivo residence time, in-vitro, and ex vivo permeation studies. The evaluation parameters of the tablets were within the acceptable Pharmacopoeial limits. However, the swelling and bio-adhesive time were increased with increasing polymer concentrations. The in-vitro release research shown that buccal tablets with sodium carboxy methyl cellulose (Na-CMC) exhibited a higher release than all other formulations and have been considered as optimized CC formulation. The release mechanism from kinetic methods suggests that the drug release follows zero-order kinetics with a diffusion mechanism. Further, in-vivo research in animal fashions is required to prove the bioavailability performance of the formulation. Keywords: Candesartan cilexetil, mucoadhesive buccal tablets, first-pass metabolism, bioavailability.

scholarly journals FORMULATION, IN VITRO AND EX VIVO CHARACTERIZATION OF MUCOADHESIVE BUCCAL TABLETS FOR ANTIHYPERTENSIVE DRUG

2018 ◽  
Vol 11 (8) ◽  
pp. 402 ◽  
Author(s):  
Himabindu Peddapalli ◽  
Vasudha Bakshi ◽  
Narender Boggula
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Surface Ph ◽  
Ex Vivo Permeation ◽  
First Pass Metabolism ◽  
First Pass ◽  
Permeation Studies ◽  
Buccal Tablets ◽  
Pass Metabolism

Objective: Olmesartan belongs to a class of angiotensin II receptor blockers. It is used in the treatment of hypertension. However, it undergoes extensive hepatic first-pass metabolism, resulting in low oral bioavailability is about 26%. The aim of this study was to prepare and evaluate the mucoadhesive buccal tablets of olmesartan with a goal to increase the bioavailability and improve the patient compliance.Methods: Mucoadhesive buccal tablets were prepared by a direct compression technique using mucoadhesive polymers such as hydroxypropyl methylcellulose (HPMC K4M), sodium carboxymethylcellulose (SCMC), and Carbopol 934P. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, swelling index, drug content uniformity, in vitro drug release, ex vivo mucoadhesive strength, ex vivo mucoadhesive time, and ex vivo permeation studies. The release kinetics was calculated to determine the drug release mechanism. Results: The physicochemical properties of all the formulations were shown to be within the limits. The optimized buccal tablets F2, F7, and F11 showed satisfactory drug release rates with the diffusion controlled mechanism. Optimized buccal tablets developed for olmesartan possess reasonable mucoadhesive strength, mucoadhesive time, and surface pH was in an acceptable salivary pH 6.76±0.28–6.89±0.34. The ex vivo permeation studies for optimized tablets were shown satisfactory drug permeation and could meet the target flux 0.991 mg h−1cm−2.Conclusion: The obtained results could be used as a platform to develop the buccal delivery of this drug, which bypasses the first-pass metabolism and results in the improvement of bioavailability. Hence, the present study concludes that the olmesartan could be delivered through the buccal route.

scholarly journals Design and Evaluation of Metoprolol Tartrate Containing Buccal Tablets

2012 ◽  
Vol 10 (2) ◽  
pp. 101-108
Author(s):  
D Nagendrakumar ◽  
S B Shirsand ◽  
MS Para ◽  
CK Makadia
Keyword(s):  
Sodium Alginate ◽  
Methyl Cellulose ◽  
Metoprolol Tartrate ◽  
Matrix Layer ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Carbopol 934P ◽  
Pass Metabolism

Metoprolol tartrate is a selective ?-1 adrenergic antagonist used in the treatment of the cardiovascular system, especially hypertension. It is readily and completely absorbed from the gastrointestinal tract but is subjected to considerable first- pass metabolism having half-life of 3 to 4 hr. It has 12% oral bioavailability. These physicochemical properties of metoprolol tartrate (undergoing considerable first- pass metabolism, low molecular weight) make it suitable candidate for administration by buccal route. Bilayered buccal tablets of metoprolol tartrate were prepared by direct compression method using combinations of polymers (carbopol 934p along with sodium carboxy methyl cellulose, sodium alginate and hydroxy propyl methyl cellulose K4M), using mannitol as a channeling agent and ethyl cellulose as a backing layer. The tablets were evaluated for physical and biological parameters. Among the 15 formulations, the formulation FA1 containing sodium alginate (34.00% w/w of matrix layer), Carbopol 934p (6.0% w/w of matrix layer) and mannitol (channeling agent, 8.0% w/w of matrix layer) was found to be promising, which showed t25%, t50%, t70% values of 0.42, 2.45, 4.48 hr respectively and in vitro drug release    of 86.04% in 8 hr along with satisfactory bioadhesive strength (5.00±0.10 g). Stability studies on the promising formulations indicated that there are no significant changes in drug content and in vitro dissolution characteristics (p<0.05). Infra-redspectroscopic studies indicated that there are no drug-excipient interactions. The prepared buccal tablets of metoprolol tartrate could stay in the buccal cavity for a longer period of time, which indicate a potential use of mucoadhesive tablets of metoprolol tartrate for treating blood pressure.   DOI: http://dx.doi.org/10.3329/dujps.v10i2.11787   Dhaka Univ. J. Pharm. Sci. 10(2): 101-108, 2011 (December)    

Formulation and Characterization of Eplerenone Mucoadhesive Buccal Tablets

2021 ◽  
pp. 3097-3103
Author(s):  
Harini Amballa ◽  
Navaneetha Kaluva ◽  
Sree Giri Prasad Beri ◽  
Krishna Mohan Chinnala ◽  
Mayuri Konda
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Release System ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Pass Metabolism

Mucoadhesive drug release system is a preferably unidirectional release system where mucosal epithelial exterior is enclosed by the mucus deposit that interacts with the bio-adhesive drug delivery system and swelling time of the buccal dosage form which is amplified by mucin molecules at the location of administration. Eplerenone is an Anti-hypertensive drug that undergoes hepatic first pass metabolism and shows 69% of bioavailability. In order to bypass the hepatic first pass metabolism the drug is designed to be delivered through buccal cavity to avoid the first pass metabolism. Eplerenone buccal tablets were formulated by using direct compression method with different polymers like HPMC K 100M, Carbopol 934P, Carbopol 974P, Xantham Gum, Eudragit L100 and NaCMC in various concentrations and compositions. Incompatibility complications were not observed from the FTIR spectrums. The formulated and prepared buccal solid dosage forms were evaluated for pre-compressions and post- compression parameters such as hardness, weight variation, thickness, friability, surface pH, swelling index, in-vitro dissolution studies, drug content uniformity, mucoadhesion strength and mucoadhesion time. Evaluation results of formulation F12 are proven to be the optimal formulation showing highest mucoadhesion time, mucoadhesion strength and in-vitro drug release for prolonged period of time about 8 hours. Eplerenone is best delivered through buccal drug delivery system to enhance its oral bioavailability and bypass the hepatic first pass metabolism.

Formulation Development and In Vitro Evaluation of Buccal Tablets of Ramipril

2020 ◽  
Vol 987 ◽  
pp. 83-87
Author(s):  
D.Nagasamy Venkatesh ◽  
Raman Rajeshkumar ◽  
Roan Ngoc Anh Huy
Keyword(s):  
Systemic Circulation ◽  
Formulation Development ◽  
Compression Technique ◽  
Zero Order Kinetics ◽  
Weight Variation ◽  
First Pass Metabolism ◽  
First Pass ◽  
Buccal Tablets ◽  
Pass Metabolism

The main objective of the present investigation was to develop buccal tablets of ramipril, to bypass the first pass metabolism and to improve its oral bioavailability. Ramipril, an ACE inhibitor used in the treatment of hypertension undergoes extensive first pass metabolism and about 25% of the drug reaches the systemic circulation. A unidirectional, bilayered mucoadhesive tablet of ramipril was prepared using HPMC as polymer by direct compression technique. Initially, a backing layer was made by using ethyl cellulose, onto which the drug containing layer as placed and recompressed to get a bilayered tablet. The buccal tablets were evaluated for various parameters such as weight variation test, thickness, hardness, friability, in vitro swelling studies, in vitro mucoadhesion study and in vitro dissolution study. Among the different formulation, the formulation (F1) prepared using 5% HPMC as polymer exhibited satisfactory performance over the other batches and considered as an ideal batch. The release of the drug from the tablets exhibited zero order kinetics and the mechanism of release was governed by diffusion process.

scholarly journals Predicting Intestinal and Hepatic First-Pass Metabolism of Orally Administered Testosterone Undecanoate

2020 ◽  
Vol 10 (20) ◽  
pp. 7283 ◽  
Author(s):  
Atheer Zgair ◽  
Yousaf Dawood ◽  
Suhaib M. Ibrahem ◽  
Hyun-moon Back ◽  
Leonid Kagan ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Hepatic Metabolism ◽  
Hydrolysis Time ◽  
Testosterone Undecanoate ◽  
Main Site ◽  
Cell Homogenate ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

The bioavailability of orally administered drugs could be impacted by intestinal and hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug of testosterone, is significantly subjected to first-pass metabolism. However, the individual contribution of intestinal and hepatic first-pass metabolism is not well determined. Therefore, the aim of the current study was to predict the metabolic contribution of each site. The hydrolysis–time profiles of TU incubation in human liver microsomes and Caco-2 cell homogenate were used to predict hepatic and intestinal first-pass metabolism, respectively. The in vitro half-life (t1/2 inv) for the hydrolysis of TU in microsomal mixtures was 28.31 ± 3.51 min. By applying the “well-stirred” model, the fraction of TU that could escape hepatic first-pass metabolism (FH) was predicted as 0.915 ± 0.009. The incubation of TU in Caco-2 cell homogenate yielded t1/2 inv of 109.28 ± 21.42 min, which was applied in a “Q gut” model to estimate the fraction of TU that would escape intestinal first-pass metabolism (FG) as 0.114 ± 0.02. Accordingly, only 11% of the absorbed fraction of TU could escape intestinal metabolism, while 91% can pass through hepatic metabolism. Hence, compared to the liver, the intestinal wall is the main site where TU is significantly metabolised during first-pass effect.

scholarly journals Optimization of ThermoreversibleIn SituNasal Gel of Timolol Maleate

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Swati Jagdale ◽  
Nirupama Shewale ◽  
Bhanudas S. Kuchekar
Keyword(s):  
Drug Release ◽  
Factorial Design ◽  
Ex Vivo ◽  
Nasal Delivery ◽  
Poloxamer 407 ◽  
Timolol Maleate ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Nasal route had shown better systemic bioavailability due to its large surface area, porous endothelial membrane, high total blood flow, and avoidance of first-pass metabolism. Timolol maleate is a beta blocker used primarily in the treatment of hypertension. Drug undergoes extensive hepatic first-pass metabolism (80%). The drug has half-life of 4 hrs. Oral bioavailability of timolol maleate is 61%. The aim of the present study was to optimize controlled releasein situnasal delivery for timolol maleate. HPMC and Poloxamer 407 were selected as polymer in formulation of thermoreversiblein situnasal gel. Optimization was carried out using 32factorial design. It was observed that formulations f1 and f4 revealed the highest % drug release, that is, 93.57% and 91.66%, respectively. Factorial design study indicated that the drug release and viscosity were most significant dependent factors.Ex vivodiffusion study through nasal mucosa indicated 67.26 ± 2.10% and 61.07 ± 2.49% drug release for f1 and f4 formulations. f1 was the optimized batch. This batch thus can act as a potential nasal delivery with enhanced bioavailability for the drug.

An in Vitro Digestion Test That Reflects Rat Intestinal Conditions To Probe the Importance of Formulation Digestion vs First Pass Metabolism in Danazol Bioavailability from Lipid Based Formulations

2014 ◽  
Vol 11 (11) ◽  
pp. 4069-4083 ◽  
Author(s):  
Mette U. Anby ◽  
Tri-Hung Nguyen ◽  
Yan Yan Yeap ◽  
Orlagh M. Feeney ◽  
Hywel D. Williams ◽  
...  
Keyword(s):  
In Vitro Digestion ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

scholarly journals Gastroretentive drug delivery system of a lipid lowering agent

2013 ◽  
Vol 2 (9) ◽  
pp. 152-155
Author(s):  
D. Krishnarajan ◽  
N. Senthil Kumar ◽  
Rajesh Yadav
Keyword(s):  
Guar Gum ◽  
Lipid Lowering ◽  
In Vitro Dissolution ◽  
Wet Granulation ◽  
Natural Polymers ◽  
First Pass Metabolism ◽  
First Pass ◽  
Mucoadhesive Tablets ◽  
Pass Metabolism

The objective of this study was to develop mucoadhesive tablets of Simvastatin using natural polymers. Simvastatin has short biological half-life and high first pass metabolism hence which was designed to increase the gastric residence time which prolong the drug release. The tablets were prepared by wet granulation technique using Carbopol-934, guar gum, xanthine gum and chitosin as polymers. Formulations were evaluated for different parameters like hardness, friability, uniformity of weight, swelling characteristics, in vitro dissolution and kinetic studies. The dissolution was carried out for 12 hours in which the formulation with guar gum has shown highest dissolution release profile (F9). Thus the present study concludes that mucoadhesive tablets of simvastatin can be a good way to pass the extensive hepatic first pass metabolism and to improve the bioavailability of simvastatin.DOI: http://dx.doi.org/10.3329/icpj.v2i9.16077 International Current Pharmaceutical Journal, August 2013, 2(9): 152-155

scholarly journals Formulation and Evaluation of Orodispersible Tablet of Atorvastatin Calcium by Using Hibiscus rosa sinesis Mucilage as Natural Superdisintegrant

2019 ◽  
Vol 9 (6) ◽  
pp. 90-94
Author(s):  
Ashish Gupta ◽  
Juhi Bhadoria ◽  
G.N. Darwhekar
Keyword(s):  
Lipid Lowering ◽  
Content Uniformity ◽  
Atorvastatin Calcium ◽  
Drug Content ◽  
Orodispersible Tablets ◽  
Orodispersible Tablet ◽  
First Pass Metabolism ◽  
First Pass ◽  
Pass Metabolism

Orodispersible tablets (ODTs), also known as fast melt, quick melts, fast disintegrating have the unique property of disintegrating in the mouth in seconds without chewing and the need of water. Oral bioavailability of Atorvastatin Calcium is low (14%) and shows extensive intestinal clearance and first-pass metabolism, which is the main cause for the low systemic availability. In the present work, orodispersible tablets of Atorvastatin calcium were prepared by direct compression method using Hibiscus rosa sinesis mucilage as natural superdisintegrant with a view to enhance patient compliance and to avoid hepatic first pass metabolism and to improve its bioavailability. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water-absorption ratio and in-vitro dispersion time. Short-term stability studies on the promising formulation indicated that there are no significant changes in drug content and in vitro dispersion time. Keywords: Orodispersible tablet, Atorvastatin Calcium, lipid-lowering agent, Superdisintegrant, Hibiscus Rosa Sinensis, Bioavailability, solubility. 

scholarly journals Formulation and Characterization of Isradipine as Oral Nanoemulsion

2020 ◽  
Vol 29 (1) ◽  
pp. 143-153
Author(s):  
Noor A. Sadoon ◽  
Mowafaq M. Ghareeb
Keyword(s):  
Oral Administration ◽  
Phase Diagrams ◽  
Polydispersity Index ◽  
Light Transmittance ◽  
Drug Content ◽  
First Pass Metabolism ◽  
First Pass ◽  
Nano Emulsion ◽  
Pass Metabolism

        Isradipine related to dihydropyridine (DHP) class of calcium channel blockers (CCBs). It is  used to treat hypertension, angina pectoris, as well as Parkinson disease. It goes under the BCS class II drug (low solubility-high permeability). The drug will experience extensive first-pass metabolism in liver, thus, oral bio-availability will be approximately15 to 24 %.         The aim of the study is preparing stable oral oil in water (o/w) nanoemulsion of isradipine to promote the colloidial dispersion of isradipine in the nano range, so that it may be absorded by intestinal lymphatic transport in order to avoid hepatic first-pass metabolism (israpidine undergoes 15-24% first pass metabolism) and increase drug bioavailability.        The solubility study was carried out in various vehicles for selecting best solvent  for dissolving isradipine. Pseudo-ternary phase diagrams is formed at (1:1, 1:2, 1:3, 1:4 and 2:1) ratios related to Smix (co-surfactant and surfactant).  There are 11 nano-emulsion was  prepared through the use of many concentrations of ( Transcutol, Tween20, and Triacetin). All formulations assessed for (in-vitro drug dissolution, pH measurement, viscosity, drug content, polydispersity index, particle size distribution, thermodynamic stability, dye test, and light transmittance). It is indicated that the extent as well as the rate of release regarding all the prepared formulations have considerably higher in comparison to that of crude drug powder. Results of characterization were explained that isradipine  nano emulsion (NE9) with S mix(1:4) : oil : deionized water (40: 5: 55) ratio was the optimized formula that has droplet size range (177.1nm), the lowest value of polydispersity index (0.12), the highest percent of drug content (99.7%) typical pH value for oral administration (5.21) , good percent of light transmittance (99.86 %), the range of viscosity (65.12 -25.2 m Pas. sec.) was suitable for oral administration, also the isradipine’s in vitro release has been considerably higher. It can be concluded that nano emulsion drug delivery system (DDS) can be considered as an encouraging method for improving the stability, dissolution and solubility of formulation. Keywords: Nanoemulsion, Isradipine  , Peudoternary phase diagrams.

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