Excerpt

ABSTRACT

The aim of the research ended up being design bilayer floating tablets of Propranolol hydrochloride and Lovastatin to provide immediate relieve Lovastatin and controlled relieve Propranolol hydrochloride. Bilayer floating tablets made up of two layers, immediate release layer and controlled release layer. Direct compression method was useful for formulation within the bilayer tablets. Temporary faster stability studies were transported round the prepared tablets. All of the formulations traveled the planet greater than 12h. Greater than 90% Lovastatin premiered within 30 min. inside the formulations. HPMC K4M and Xanthan gum retarded the discharge of Propranolol hydrochloride inside the controlled release layer for 12h. After stability studies, apparent degradation of both drugs develop nonetheless the drug content was seen to become inside the range. Diffusion exponent (n) was resolute for your formulations (.53-7). According to coefficient of correlation(R), the discharge of Propranolol hydrochloride was discovered to look at mixed release pattern of Hixson-Crowell, Korsmeyer-Peppas and matrix, except formulation F6 and F9, which adopted zero order release pattern. Record analysis states there was not aspect in in vitro release pattern within the drugs pre and publish stability studies.

Keywords and key phrases: Lovastatin, Propranolol hydrochloride, floating, bi- layer tablets.

INTRODUCTION

Hypertension and hypercholesterolemia frequently exist together and could require concomitant medications. The success and safety profile of Lovastatin succumbed the existence of antihypertensive medication was evaluated using patient subgroups identified within the Expanded Clinical Check out Lovastatin study.[1-3] Treating hypertension co-existing with hyperlipidemia is unquestionably uncovered to various kinds of drugs, like, angiotensine converting enzyme inhibitors, calcium funnel blockers, b-blockers etc.

Control of the bloodstream stream pressure was effectively achieved together therapy than individual therapy. In U.S. ever large numerous studies were conducted namely Antihypertensive and Fat Lowering Treatment to avoid Stroke Trials (ALLHAT). Several studies report that hypertension hyperlipidemia might have additive or perhaps synergistic effects. Various numerous studies conducted suggest combination therapy to cope with hypertension hyperlipidemia.[4-7] Inside our study, we’ve tried to mix Lovastatin and Propranalol hydrochloride by formulating in a bilayer tablet. Many approaches are utilized to design gastroretentive dosage forms[8,9].Incorporated in this particular are, low density floating dosage forms 10 high density dosage forms which remain at the conclusion within the stomach, bioadhesive systems 11 swelling sytems 12 hydrodynamically balanced systems 13 .Gastric retention within the drugs provide benefits of example (i) locating the drugs with narrow absorption home home home windows within the small intestinal region (ii) longer residence over time the stomach might be beneficial for local action within the upper a part of small intestine 13.

Various dosage forms are really created for gastric retention incorporated in this particular are, floating tablets 14 floating beads 15 pellets 16 floating granules 17 floating microspheres 18. The present analysis employs advancement of floating bilayer tablet for several release pattern of Lovastatin and Propranolol hydrochloride using gas generating agent. Propranolol hydrochloride, a non-selective beta adrenergic blocking agent remains broadly present in treating angina pectoris, hypertension and lots of other cardiovascular disorders. The treatment is water soluble and possesses half info on three.4 h. It’s bioavailability is 5-50% 19 .Therefore, it had been selected as being a drug its gastro-retentive formulation. Lovastatin, a HMG Co-A reductase inhibitor is broadly present in treating hyperlipidemia. The drug has very short half existence of merely one.1-1.7h with very less bioavailability 5-50% [20, 21]. The bilayer tablet made up of immediate release layer of Lovastatin and controlled release layer of Propranolol hydrochloride. The discharge kinetics of Propranolol hydrochloride was examined using different mathematical models. Faster stability studies were transported round the prepared tablets 22. Inside the finish of stability studies, tablets were evaluated for in vitro drug release, floating characteristics, drug content along with other physicochemical parameters.

Techniques And Materials

Propranolol hydrochloride was acquired from CIPLA Limited. (Mumbai, India).Lovastatin is a generous gift from Remedy Biotech (Chandigarh, India). HPMC K4M and Xanthan gum(XG) were acquired as gift samples from Remedy Biotech (Chandigarh, India).Sodium starch glycolate(SSG), was acquired from Okasa Pharma Limited. (Satara, India).Tablettose 80 was received just like a present sample from Wockhardt Limited.,(Aurangabad, India).Many other materials were bought in commercial sources:Magnesium stearate(Loba chemicals, Mumbai, India), di-calcium phosphate(S.D.Fine chemicals,Mumbai,India), Sodium bi carbonate(Research lab, Mumbai, India).

Method

Preparation of Bilayer Floating Tablets

Bilayer floating tablets were produced by direct compression method employing sodium starch glycolate as superdisintegrant, HPMC K4M and XG as rate controlling polymers, individuals who’re as gas generating agent. The optimum concentrations of above ingredients were developed under experimental conditions and based on trial preparation within the tablets. Preparation of bilayer floating tablets had two steps: i) preparation of controlled release layer

The ingredients (Table 1) were precisely considered and were put into the blender in climbing order. The powder mix was blended for 20 five min. to possess uniform distribution of drug within the formulation. 300 mg within the powder mix was considered precisely and provided to the die of single punch machinery (Cadmach, Ahemedabad, India.) and compressed at 1.5 N compression pressure using 10 mm concave punches. ii) preparation of immediate release layer

The ingredients (Table 1) were precisely considered and were put into the blender in climbing order. The powder mix was blended for 20 five min. to possess uniform distribution of drug within the formulation. 100 mg within the powder mix was considered precisely and presented to the controlled release layer and compressed at 3 N compression pressure using 10 mm concave punches.

Floating characteristics

Floating characteristics within the prepared formulation were based on using USP 23 paddle apparatus 19 (Electrolab TDT-06P, Mumbai, India) at paddle speed of fifty revolutions each minute in 900 ml .1N HCl (pH 1.2) at 37±0.20C for 25-four h. Time between introduction of tablet that is buoyancy across the simulated gastric fluid (floating lag time) along with the time where the dosage form remain buoyant (floating duration) were measured. Also, the integrity within the tablet during study was observed visually (matrix integrity).

Drug content

Propranolol HCl

Twenty tablets were precisely considered and average weight was calculated. These tablets were ground having a fine powder. An precisely considered tablet powder similar to 120 mg of Propranolol hydrochloride was dissolved in methanol and volume should 100 ml. The answer was filtered through Whatmann filter paper No.41. An aliquot of merely one ml was taken and diluted to 24 ml. Further, 1 ml by using this diluted stock solution was taken and diluted to 10 ml. For the estimation of Propranolol hydrochloride inside the sample solution absorbance of sample solution was recorded at 255nm and 287nm and the amount of Propranolol hydrochloride within the sample solution was acquired inside the calibration curve. The calibration curve for Propranolol hydrochloride was plotted using absorbance of 10 standard solution of Propranolol hydrochloride round the concentration selection of 1mcg/ml to 10mcg/ml. Lovastatin doesn’t have absorbance at 255nm and 287nm.

Lovastatin

Twenty tablets were precisely considered and average weight was calculated. These tablets were ground having a fine powder. An precisely considered tablet powder similar to 50 mg of Lovastatin was dissolved in methanol and volume should 100 ml. The answer was filtered through Whatmann filter paper No.41. An aliquot of merely one ml was taken and diluted to 100 ml. For the estimation of Lovastatin inside the sample solution a noticable difference spectrophotometric method was created and validated to get rid of interference of absorbance by Propranolol hydrochloride within the sample solution. The calibration curve for estimation of Lovastatin was acquired by plotting difference of absorbance at 247nm and 312nm of 10 mixed standard solution containing 1mcg/ml to 10 mcg/ml of Lovastatin against its concentration.

Drug release

The discharge of Propranolol hydrochloride and Lovastatin from various formulations was resolute using USP 23 paddle apparatus2 23 (Electrolab TDT-06P, Mumbai, India) under sink conditions. The dissolution medium was 900 ml .1N HCl (pH 1.2) at 37±0.20C obtaining a stirring speed of fifty revolutions each minute. For every formulation, the research was transported in triplicate. The discharge data was examined to look at release kinetics using zero order, Korsmeyer-Peppas and Higuchi equations [24, 25].

Hardness

Hardness within the prepared formulations was resolute using Monsanto hardness tester (n=10) 26 .

Stability

To evaluate the drugs and formulations, temporary stability studies were transported out. All of the formulation samples, sealed in aluminium packaging coated inside with polyethylene, as well as other replicates were stored in humidity chamber maintained at 400C and 75% RH for a lot of a few days. Inside the finish within the studies, samples were examined for drug content, floating characteristics, hardness plus vitro dissolution studies. The research was transported in triplicate.

DSC studies

Thermal analysis was transported out using Mettler Toledo 821e DSC (Europe). Named was ground to powder and 1-2 mg sample was hermetically sealed in a aluminum pan and heated in the constant rate of 100C/min, round the temperature selection of 500C-5000C. Inert atmosphere was maintained by purging nitrogen gas inside the flow rate of 20mL/min.

Assessment of Similarity factor

The similarity factor (f2 factor) was applied to evaluate dissolution profiles of Propranolol hydrochloride. The in vitro dissolution release profile within the formulations before stability studies were regarded as reference plus vitro dissolution release profile within the formulations after stability studies were regarded as test. Similarity factor was calculated using PCP Disso software. The f2 factor could be a logarithmic reciprocal square root transformation from the sum squared error. The f2 factor enables you to quantitate agreement between two dissolution profiles. Dissolution testing was conducted beneath the identical conditions. The of f2 among fifty to at least one hundred shows similarity in dissolution profile with regard.

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Record Analysis

Analysis of variance (ANOVA) was performed to discover aspect in drug released at 12h, floating lag serious amounts of drug content all formulations. Student’s‘t’ test was put on assess improvement inside the discharge pattern within the drug pre and publish stability studies.

RESULTS

Floating characteristics

All of the formulations traveled the planet greater than 12h with lag length of 16 min. During floating duration formulations maintained matrix integrity (Table 2). Swelling within the tablets was observed, which added the floating capacity for the formulations. A 5% power sodium bi carbonate was seen to become optimum for low lag serious amounts of prolonged floating duration. Floating duration and lag previously seen is the functions of amount of polymers incorporated within the formulations

Drug content

Propranolol hydrochloride (99.36%-102%) and Lovastatin (95.9%-102.02%) content develop inside the specifications. Additives within the formulations was missing any impact on the drug content (Table 2).

In vitro drug release

Lovastatin

Immediate release layer of bilayer floating tablet disintegrated liberating Lovastatin. All of the formulations liberated greater than 90% Lovastatin within 30 min. A 8% power sodium starch glycolate was seen to become optimum. Disintegration within the immediate release layer was missing any impact on the options within the controlled release layer.

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