DEVELOPMENT AND CHARACTERIZATION OF TACROLIMUS TABLET FORMULATIONS FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Optimization of ThermoreversibleIn SituNasal Gel of Timolol Maleate

Scientifica ◽

10.1155/2016/6401267 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 10

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.

Download Full-text

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.

Download Full-text

Effect of various Polymers on Drug Release from Mucoadhesive Tablets of Cefixime Trihydrate

Research Journal of Pharmaceutical Dosage Forms and Technology ◽

10.52711/0975-4377.2021.00030 ◽

2021 ◽

pp. 167-173

Author(s):

Kumara Swamy Samanthula ◽

Agaiah Goud Bairi ◽

Shobha Rani Satla ◽

Mahendra Kumar CB

Keyword(s):

Drug Release ◽

Diffusion Mechanism ◽

In Vitro Release ◽

In Vitro Dissolution ◽

Content Uniformity ◽

First Pass Metabolism ◽

First Pass ◽

Mucoadhesive Tablets ◽

Pass Metabolism

Cefixime trihydrate (CT) is a third-generation cephalosporin antibiotic and is used in the management of various infections caused by Gram +ve as well as Gram – ve bacteria. It has a plasma half-life of 3-4 h. It has poor oral bioavailability due to hepatic first pass metabolism. Hence, an attempt was made to develop CT mucoadhesive tablets for buccal delivery to avoid first-pass metabolism and improved oral delivery. CT mucoadhesive tablets developed using HPMC K4M, Na-CMC, guar gum and chitosan as rate controlling polymers and mucoadhesive agent, respectively and compressed by direct compression method. The prepared CT mucoadhesive tablets were evaluated for hardness, weight variation, thickness, friability, drug content uniformity, assay, mucoadhesive strength and in vitro release. From the results, all the evaluated parameters were within the pharmacopoeial limits. The in-vitro dissolution studies indicated that the CTmucoadhesive tablets formulation (F2) showed 99.7±1.4 % of drug release after 8 h and chose as the optimized formulation. The kinetic models suggest that the drug release follows Higuchi’s kinetics and tablets drug release was controlled by a diffusion mechanism.

Download Full-text

Novel core in cup (In-lay) tablets of lamotrigine for mucoadhesive drug delivery system

International Current Pharmaceutical Journal ◽

10.3329/icpj.v5i2.26440 ◽

2016 ◽

Vol 5 (2) ◽

pp. 9-13

Author(s):

K. Srinija ◽

P.K. Lakshmi

Keyword(s):

Drug Release ◽

Orthogonal Array ◽

Xanthan Gum ◽

Pharmaceutical Journal ◽

Physical Parameters ◽

Bcs Class Ii ◽

Zero Order Kinetics ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Lamotrigine a BCS class II drug used in treatment of epilepsy has several disadvantages when taken orally (first pass metabolism and increased Cmax). The aim of the study is to design core in cup (In lay) buccoadhesive tablets which aims for controlled, unidirectional release, increased patient compliance and decreased side effects. The present study involves the preparation of core in cup tablets containing release retarding polymers like sodium alginate, xanthan gum and HPMC E 15LV in core and HPMC K 15M in cup for mucoadhesion. L9 orthogonal array Taguchi design was constructed for the study. The dependent variable studied for L9 orthogonal array Taguchi runs include % drug release from which the formulation with highest S/N ratio was optimized. All the runs were evaluated for physical parameters, drug release, mucoadhesive studies and assay. L1, L2, L4 and L8 formulations showed controlled release for up-to 8 hours with good assay values. The model dependent kinetics showed zero order kinetics with super case II transport and Hixson Crowell mechanism which indicates unidirectional drug release.Srinija and Lakshmi, International Current Pharmaceutical Journal, January 2016, 5(2): 9-13

Download Full-text

Design, Development and Characterization of Nifedipine Microspheres

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i3.2627 ◽

2019 ◽

Vol 9 (3) ◽

pp. 138-146

Author(s):

Arun Kumar Chalamalasetty ◽

Boggula Narender ◽

Bolledla Nirosha ◽

Bakshi Vasudha ◽

Peddapalli Himabindu

Keyword(s):

Particle Size ◽

Drug Release ◽

Oral Bioavailability ◽

Ethyl Cellulose ◽

Hydroxypropyl Methylcellulose ◽

Prolonged Release ◽

Design Development ◽

First Pass Metabolism ◽

First Pass ◽

Pass Metabolism

Back ground: Nifedipine is a calcium channel blocker and is used in treatment of angina of angina pectoris and hypertension. Nifedipine readily and almost completely absorbed from GIT, but undergoes first pass metabolism, resulting in low oral bioavailability is about 50%. Aim: The aim of the present study was to prepare and evaluate the microspheres of nifedipine with a goal of improving the bioavailability and giving a prolonged release of drug. Method: Emulsification (o/w) solvent evaporation method was employed in the preparation of nifedipine microparticles using ethyl cellulose and combination of ethyl cellulose and hydroxypropyl methylcellulose as the polymers. Results: FT-IR spectra of physical mixture showed no significant shifting of the peaks therefore it reveals that the drug is compatible with the polymer used. The percentage yield obtained in all the formulations was good and in the range of 59.25-94.44%. Among all the formulations, formulation with combination of ethyl cellulose and hydroxypropyl methylcellulose polymers M9 showed high amount of drug release i.e. (91.23%) in 12hrs. Drug release from microspheres with small mean particle size was faster than those with large mesh particle size and followed Higuchi model of kinetics. Conclusion: The obtained results could be used as essence to develop microspheres, which bypasses first-pass metabolism and results in the improvement of bioavailability. Hence, the present study has been a satisfactory attempt to formulate microspheres of nifedipine, with a view of improving its oral bioavailability and giving a prolonged release of drug. Keywords: Microspheres, nifedipine, hydroxypropyl methylcellulose E5, ethyl cellulose.

Download Full-text

Formulation and Physicochemical Characterization of Buccal Mucoadhesive Films Containing Alfuzocin Hydrochloride

Journal of Advances in Medical and Pharmaceutical Sciences ◽

10.9734/jamps/2020/v22i230155 ◽

2020 ◽

pp. 9-20

Author(s):

Abikesh P. K. Mahapatra ◽

Sonia P. Nagvenkar ◽

Rajashree Gude

Keyword(s):

Drug Release ◽

In Vitro Release ◽

Zero Order ◽

Content Uniformity ◽

Ideal System ◽

First Pass Metabolism ◽

Folding Endurance ◽

First Pass ◽

Pass Metabolism

The buccal region of oral cavity is a interesting target for the drug of choice administration. To increase prevent first pass metabolism and bioavailability, Alfuzocin Hydrochloride is embedded in buccal film for a sustained release over a period of 8 hours. The purpose of this study was to develop formulations and systematically evaluate in vitro performances of buccoadhesive films of Alfuzocin hydrochloride using the polymers HPMC K100M, Sodium Alginate and Chitosan. The films were provided with a backing layer of Eudragit RS100 so as to get an unidirectional release pattern. The films were evaluated for their physical characteristics like weight, thickness, content uniformity, folding endurance, bioadhesive strength, surface pH, in vitro drug release, ex vivo buccal permeation and XRD studies. The films, which were prepared by the solvent casting method, were smooth and elegant in appearance; uniform in thickness, weight, and drug content; and showed good folding endurance. The mechanical properties reveal that the formulations were found to be strong but not brittle. The in vitro release data were fit to different equations and kinetic models viz. zero order, first order, higuchi’s plot and peppas plot. The best mucoadhesive performance and matrix controlled release was exhibited by the formulation A7 (2% HPMC K100 M and 2% Chitosan). The correlation coefficient value (r) indicates, the kinetic of drug release was zero order. Stability study of optimized films was done and it was found that both drug and buccal films were stable. It can be concluded that the present buccal formulation can be an ideal system to improve the bioavailability of the drug by avoiding hepatic first-pass metabolism.

Download Full-text