FORMULATION AND EVALUATION OF BILAYER TABLETS OF TWO INCOMPATIBLE DRUGS AMLODIPINE BESILATE AND LOSARTAN POTASSIUM

Objective: The aim of this research work was to develop and evaluate a bilayer formulation of losartan potassium and metformin hydrochloride for the treatment of diabetic patients with hypertension. In the present study, losartan potassium as immediate-release (IR) layer and metformin hydrochloride as a sustained-release (SR) layer were selected. Methods: The polymers selected were fenugreek gum, sweet potato starch, and ispaghula gum as natural disintegrants for IR layer and guar gum, xanthan gum, and pectin for SR layer. Bilayer tablets were developed by employing the two layers. Results: For IR layer, L4 formulation with 5% ispaghula gum as natural disintegrant showed 98.94% drug release was selected as an optimized layer. For sustained layer, F2 formulation with 18.75% guar gum as drug retardant showed 97.17% drug release was selected as optimized layer. Optimized formulation followed zero-order kinetics. When the release data was plotted into Higuchi and Korsmeyer-Peppas equations, then it was confirmed that the optimized formulation exhibited a Fickian diffusion type drug release. Conclusion: Tablets prepared with 5% ispaghula gum and 18.75% guar gums as drug retardants were found to be useful for bilayer tablet formulation with desired drug release characteristics.

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Development and Evaluation of Controlled Release Bilayer Tablets of Hydrochlorothiazide and Losartan Potassium

Journal of Pharmacy and Nutrition Sciences ◽

10.6000/1927-5951.2015.05.01.13 ◽

2015 ◽

Vol 5 (1) ◽

pp. 84-94

Author(s):

Manoj Mishra ◽

◽

Dubey Deepti ◽

Upamanyu Neeraj

Keyword(s):

Controlled Release ◽

Losartan Potassium ◽

Bilayer Tablets

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Formulation and Evaluation of Immediate Release Bilayer Tablets of Telmisartan and Hydrochlorothiazide

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2011.4.3.6 ◽

2011 ◽

Vol 4 (3) ◽

pp. 1477-1483

Author(s):

Natarajan R ◽

N Patel ◽

Rajendran N N ◽

M Rangapriya

Keyword(s):

Antihypertensive Drugs ◽

In Vitro Release ◽

Immediate Release ◽

Wet Granulation ◽

Physical Parameters ◽

Dissolution Profile ◽

Formulation Development ◽

Sodium Starch Glycolate ◽

Bilayer Tablets

The main goal of this study was to develop a stable formulation of antihypertensive drugs telmisartan and hydrochlorothiazide as an immediate-release bilayer tablet and to evaluate the dissolution profile in comparison with a reference product. The formulation development work was initiated with wet granulation. Telmisartan was converted to its sodium salt by dissolving in aqueous solution of sodium hydroxide to improve solubility and drug release. Lactose monohydrate and microcrystalline cellulose were used as diluents. Starch paste is prepared in purified water and was used as the binder. Sodium starch glycolate is added as a disintegrating agent. Magnesium stearate was used as the lubricant. The prepared granules were compressed into a double-layer compression machine. The tablets thus formulated with higher proportion of sodium starch glycolate showed satisfactory physical parameters, and it was found to be stable and in vitro release studies are showed that formulation (F-T5H5) was 101.11% and 99.89% respectively. The formulation T5H5 is further selected and compared with the release profile of the innovator product, and was found to be similar (f2 factor) to that of the marketed product. The results suggest the feasibility of developing bilayer tablets consisting of telmisartan and hydrochlorothiazide for the convenience of patients with hypertension.

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Formulation of Oral Mucoadhesive Tablets using Mucilage Isolated from Buchanania lanzan spreng Seeds

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2014.7.2.11 ◽

2014 ◽

Vol 7 (2) ◽

pp. 2494-2503

Author(s):

Sudarshan Singh ◽

Ayaz Ahmad ◽

Sunil Bothara B

Keyword(s):

Drug Delivery ◽

Guar Gum ◽

Physical Property ◽

Flow Property ◽

Relative Effect ◽

Losartan Potassium ◽

In Vitro Dissolution ◽

Wet Granulation ◽

Microbial Count

The present study was taken to formulate and evaluate mucilage obtained from Buchanania lanzan spreng seeds (BL) belonging to family anacardiacea for oral mucoadhesive drug delivery system containing losartan potassium. Physiochemical characteristics of mucilage, such as swelling index, microbial count, viscosity, hydration capacity, flow property, and pH were studied. The mucilage was evaluated for its mucoadhesive properties in compressed tablet, containing losartan potassium. Granules were prepared by wet granulation process using polyvinylpyrrolidone as binding agent. Mucilage was used in four different concentrations i.e., 21, 42 and 55% w/w. The tablet were prepared and evaluated for its physical property. Further, in vitro dissolution and swelling index was determined. The property of bioadhesive strength of isolated mucilage was compared with Guar gum and HPMC E5LV, which was used as standard mucoadhesive agent concentration. Bioadhesive strength of the tablet was measured on the modified physical balance. Result revealed that tablets had good physiochemical properties, and drug release was retarded as concentration of mucilage was increased. The force of adhesion was obtained 0.1238N, 0.2822N, 0.5175N, 0.8679N and 0.3983N respectively for F1, F2, F3, F4 and F5. Formulations were subjected for study the effect of agitation at different rpm. Formulation showed relative effect on release of drug from formulation. All the formulations were subjected to stability studies for three months, all formulations showed stability with respect to release pattern. In conclusions, these results indicate that the seed mucilage of BL can be a suitable excipient for oral mucoadhesive drug delivery systems.

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Utilization of a Single Experimental Design for the Optimization of Furosemide Modified-Release Tablet Formulations

Current Drug Delivery ◽

10.2174/1567201816666191029130324 ◽

2019 ◽

Vol 16 (10) ◽

pp. 931-939

Author(s):

Marilena Vlachou ◽

Angeliki Siamidi ◽

Yannis Dotsikas

Keyword(s):

Experimental Design ◽

Drug Release ◽

Burst Release ◽

Dissolution Profile ◽

Modified Release ◽

Lactose Monohydrate ◽

Bilayer Tablets ◽

Combined Design ◽

Tablet Formulations ◽

Optimal Combined Design

Background: The loop diuretic drug furosemide is widely used for the treatment of edema in various conditions, such as pulmonary, cardiac and hepatic edema, as well as cardiac infarction. Furosemide, due to its poor water solubility and low bioavailability after oral administration of conventional dosage form, is categorized as class IV in the biopharmaceutical classification system. Objective: In the case of furosemide, this release profile is responsible for various physiological problems, acute diuresis being the most serious. This adverse effect can be circumvented by the modified release of furosemide from tablet formulations compared to those forms designed for immediate release. Method: In this report, a D-optimal combined experimental design was applied for the development of furosemide containing bilayer and compression coated tablets, aiming at lowering the drug’s burst release in the acidic environment of the stomach. A D-optimal combined design was selected in order to include all requirements in one design with many levels for the factors examined. The following responses were selected as the ones reflecting better criteria for the desired drug release: dissolution at 120 min (30-40%), 300 min (60-70%) and 480 min >95%. The new formulations, suggested by the Doptimal combined design, incorporated different grades of Eudragit ® polymers (Eudragit® E100 and Eudragit® L100-55), lactose monohydrate and HPMC K15M. The dissolution profile of furosemide from these systems was probed via in vitro dissolution experiments in buffer solutions simulating the pH of the gastrointestinal tract. Results: The results indicate that the use of Eudragit® E100 in conjunction with lactose monohydrate led to 21.32-40.85 % drug release, in the gastric medium, in both compression-coated and bilayer tablets. This is lower than the release of the mainstream drug Lasix® (t=120 min, 44.5% drug release), implying longer gastric retention and drug waste minimization. Conclusion: Furosemide’s release in the intestinal environment, from compression coated tablets incorporating Eudragit® L100-55 and HPMC K15M in the inner core or one of the two layers of the bilayer tablets, was delayed, compared to Lasix®

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A Randomized, Placebo-Controlled, Double-Blind, Parallel Study of Various Doses of Losartan Potassium Compared With Enalapril Maleate in Patients With Essential Hypertension

Hypertension ◽

10.1161/01.hyp.25.6.1345 ◽

1995 ◽

Vol 25 (6) ◽

pp. 1345-1350 ◽

Cited By ~ 143

Author(s):

Alan H. Gradman ◽

Karen E. Arcuri ◽

Allan I. Goldberg ◽

Leila S. Ikeda ◽

Edward B. Nelson ◽

...

Keyword(s):

Essential Hypertension ◽

Losartan Potassium ◽

Parallel Study ◽

Double Blind ◽

Enalapril Maleate

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Investigation of the Physical, Chemical and Microbiological Stability of Losartan Potassium 5 mg/mL Extemporaneous Oral Liquid Suspension

Molecules ◽

10.3390/molecules26020301 ◽

2021 ◽

Vol 26 (2) ◽

pp. 301

Author(s):

Lisa Foley ◽

Jennifer Toney ◽

James W. Barlow ◽

Maura O’Connor ◽

Deirdre Fitzgerald-Hughes ◽

...

Keyword(s):

Shelf Life ◽

Storage Conditions ◽

Losartan Potassium ◽

Microbial Count ◽

E Coli ◽

Physical Chemical ◽

Liquid Suspension ◽

Oral Liquid ◽

Microbiological Stability ◽

Stability Data

Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady’s Children’s Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80–81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations.

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Formulation and optimization of gastroretentive bilayer tablets of calcium carbonate using D-optimal mixture design

e-Polymers ◽

10.1515/epoly-2021-0008 ◽

2021 ◽

Vol 21 (1) ◽

pp. 057-071

Author(s):

Manasa Moganti ◽

Shivakumar H. Nanjappa

Keyword(s):

Calcium Carbonate ◽

Optimization Technique ◽

Lag Time ◽

Mixture Design ◽

Burst Release ◽

Bilayer Tablets ◽

Absorption Window ◽

Upper Gastrointestinal ◽

Gastric Retention Time

Abstract Gastroretentive bilayer tablets of calcium carbonate (CC) were developed using D-optimal mixture design. The effect of formulation factors such as levels of HPMC K100 M (X1), sodium bicarbonate (X2), and HPMC E15 LV (X3) on responses like floating lag time (R1) and release of CC at 1 h (R2) and 6 h (R3) was elucidated. The optimized formulations developed by numerical optimization technique were found to have short floating lag time (2.85 ± 0.98 min), minimum burst release (27.02 ± 1.18%), and controlled yet near complete release (88.98 ± 2.75%) at 6 h. In vivo radiographic studies in rabbits indicated that optimized batch displayed a mean gastric retention time (GRT) of 5.5 ± 1 h which was significantly prolonged (P < 0.05) compared to the conventional tablets that displayed a GRT of less than 1 h. The studies proved that the gastroretentive tablets can be a promising platform to improve bioavailability of nutrients having absorption window in upper gastrointestinal tract.

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