Drug Complexation and Formulation of a Buccal Tablet

In the present work use of Beta-Cyclodextrin for inclusion of Carvedilol, an antihypertensive drug with poor solubility and high first pass metabolism was studied, in order to improve its dissolution rate. The complex prepared by kneading method was characterized by Differential Scanning Calorimetry, Fourier Transformation Infra Red Spectroscopy and X-Ray Diffractometry along with the plain drug and physical mixture. The drug so complexed was incorporated into a buccal dosage form to by pass first pass metabolism to improve its bioavailability. The buccal tablets containing complex showed reasonable mucoadhesive strength. The dissolution and permeability across pig buccal mucosa were improved in case of tablets containing the complex as compared to plain drug tablet. Key words: Carvedilol; Beta-Cyclodextrin; Complexation; Dissolution; Characterization; Permeation. DOI: 10.3329/bjsir.v45i2.5709Bangladesh J. Sci. Ind. Res. 45(2), 123-128, 2010

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Development, Characterization and Optimization of Mucoadhesive Tablet for Buccal Delivery of Domperidone

Drug Delivery Letters ◽

10.2174/2210303108666181108120840 ◽

2019 ◽

Vol 9 (1) ◽

pp. 37-49

Author(s):

Jagdale Sachin ◽

Panbude Aishwarya ◽

Navasare Priya

Keyword(s):

Drug Release ◽

Factorial Design ◽

Research Work ◽

Wet Granulation ◽

Buccal Delivery ◽

Scanning Calorimetry ◽

Mucoadhesive Polymers ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Background and Objective: Upon oral administration domeperidone is rapidly absorbed, but subjected to the first pass effect which lowers systemic bioavailability to 15%. Mucoadhesive tablet can remain attached to buccal mucosa and becomes capable of bypassing hepatic first-pass metabolism to improve absorption directly into systemic circulation. The present research work was carried with an aim to develop, evaluate and optimize mucoadhesive tablet containing domperidone (DOME) for buccal delivery using different bio-adhesive polymeric combinations. </P><P> Methods: The buccal tablets were formulated by wet granulation method using isopropyl alcohol. The preliminary formulations were prepared using combinations of HPMC K4, HPMC K15, HPMC K100, HPMC E5 as mucoadhesive polymers. 32 full factorial design was applied to determine the effect of independent variables like concentration of mucoadhesive polymers (HPMC K15 and HPMC K100) over dependent variables like mucoadhesive properties (swelling index, bioadhesive strength and in vitro drug release). The prepared mucoadhesive tablets were evaluated for their tablet properties and mucoadhesive properties. The interactions between drug and polymers were studied by Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC). </P><P> Results: All formulations of factorial design showed satisfactory physicochemical, mechanical and bioadhesive characteristics. The formulation F9 exhibited maximum cumulative drug release, mucoadhesive strength and swelling index. Conclusion: The developed buccal tablet of domperidone might prove alternative to bypass the hepatic first pass metabolism and to avoid degradation which in turn may result in reducing the frequency of administration. Thus, mucoadhesive tablet of domeperidone may become viable alternative overcoming the side effects; achieving greater therapeutic effectiveness and improving the patient compliance.

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Formulation and Characterization of Eplerenone Mucoadhesive Buccal Tablets

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00541 ◽

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.

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

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.26126 ◽

2018 ◽

Vol 11 (8) ◽

pp. 402 ◽

Cited By ~ 1

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.

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Design and Evaluation of Metoprolol Tartrate Containing Buccal Tablets

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v10i2.11787 ◽

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)

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Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

Journal of Pharmaceutics ◽

10.1155/2013/265741 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

Arjun Narala ◽

Kishan Veerabrahma

Keyword(s):

Solid Lipid Nanoparticles ◽

Oral Bioavailability ◽

Entrapment Efficiency ◽

Lipid Nanoparticles ◽

Scanning Calorimetry ◽

Quetiapine Fumarate ◽

Solid Lipid ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism.

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

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i1-s.4547 ◽

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.

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Formulation Development and In Vitro Evaluation of Buccal Tablets of Ramipril

Materials Science Forum ◽

10.4028/www.scientific.net/msf.987.83 ◽

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.

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