Effect of Natural Polymer and Excipients on Gastro Retentive Behavior of Floating Ranitidine Tablet

Gastric emptying for dosage forms is a highly variable process, specifically for those dosage forms that have a stomach stay for more than that of conventionally prepared dosage forms. For controlled release, drugs were designed in such dosage form to drug release at the programmed rate for maintaining the particular concentration of drug-specific time period with minimal side effects. The gastric retentive system is so formulated in an attempt to retain GIT for a longer time period ultimately enhancing the retention time of the drugs in the gastric region hence increasing their potential for absorption. Many different approaches are available that protect gastric retention, including a floating drug delivery system. A floating system, a dense density- controlled them, increases the retention time of a drug in GIT. For this, we use several approaches like muco-adhesion, gas generating, high-density, and low-density systems [1,2]. Floating improves the efficacy of tablets by controlling the rate of drug release and reducing dose frequency. Floating systems can be either non-effervescent or effervescent floating drug delivery systems. The effervescent approach utilizes various polymers in providing the floating drug delivery system Hydroxy propyl methyl cellulose is a cellulose ether polymer of non-ionic nature. It may be fibrous or in granular powder form which is soluble in cold water and is. In soluble in hot water (Higuchi&Hussain,1978). HPMC has been in use as a tablet binder, as a film coater, and also to produce matrix tablets of extended-release. It is also  used  for  the synthesis of the oral controlled drug delivery system. It has excellent characteristics of compression and good swelling properties, which helps in the formation of a gel layer (external) that further control the release of the drug [4]. Floating effervescent tablets of Ranitidine HCl were formulated in this study. Pre-compression parameters such as repose angle, tapped density, bulk density, and compressibility index and after- compression parameters such as thickness, weight variation, friability, hardness, drug content, and in vitro drug release were investigated. Dissolution studies were performedin0.1N HCl solution. Moreover, FTIR was performed to investigate the drug-polymer interaction.

MATERIALS AND METHOD

1. • Chemicals: Hydroxy propyl methyl cellulose, Tartaric acid, Tara gum, Lactose, Talc (glidant) Magnesium stearate (lubricant) & sodium bicarbonate. Moreover, Hydrochloric acid, and were also procured by Merck, as the drug Ranitidine HCl. All chemicals were of analytical grades.
   • Instruments: UV spectrophotometer (shimedzu 1800), paddle (Apparatus II) dissolution apparatus, analytical weighing balance, Erweka hardness tester, vernier calipers, Roche Friabillator, and single punch tablet compression machine.
2.  Experimental Work

• Extraction and purification of Tara Gum: The Tara gum was extracted from Tara seed.

• Charaterization of Tara gum: The purified and dried extracted powder was evaluated for its micromeritis properties preformulation studies, solubility studies, swelling index, and loss on drying shown in table no.01

Extraction and purification of Tara gum:

• 1.8 kg of fresh pods from C. Spinosa dried under air flow in solar oven at 35ºC.
• Ground down and to obtain 0.9 kg of plant material.
• The plant material was extracted with ethanol (96% 4.5L) in recirculation percolator (2 times per days) over 10 days.
• The ethanol crude extract (8gm) was concentrated under vacuum trapped on silica gel and removed excess humidity at 25ºC.
• Afterwards, the ethanol extract was fractionated with the following solvents: petroleum ether(150ml); chloroform(200ml) ethanol; (200ml) and water (200ml)
• The pure Tara gum was oven dried

Table No. 01: Physiochemical Characterization of Tara gum

7. 2 Preformulation Parameter:

• Organoleptic properties

The sample of Ranitidine was identified for color, odor and taste which were found to be same as that standard parameters.

Table No. 02: Organoleptic properties of Ranitidine HCl

Identification of Drug

• By UV Spectroscopy: 10 mg drug dissolve in 100 ml of 0.1N HCL it’s an obtained stock solution of 100micrograms/ml. Then from the stock solution, 10 ml of solution is taken and the volume is made up to 100 ml with 0.1 N HCL solution and scanned under UV between 200 to 400 nm wavelength.

Figure 01: Ranitidine HCL Spectrum by UV Spectroscopy

• By Melting point determination:

Melting Point determination is one of the formulation properties in which the temperature at which it changes state from solid to liquid at atmospheric pressure. During the melting process, the solid and liquid can exist in equilibrium. The Melting point of the Ranitidine HCL drug is determined by using Melting Point Apparatus. [11]

Table No.3: Melting Point of Ranitidine HCL

• Calibration curve of Ranitidine HCl

Measurement of the spectrum of Ranitidine HCl by using UV Visible1800 Shimadzu double beam spectrophotometer. Absorbance was observed at 310nm.

• Standard stock solution

An accurately weighed quantity of Ranitidine HCl(10mg) was dissolved in 0.1N HCl to make a10 ml Solution (1000µg\ml).

• Dilutions preparation

From the standard stock solution of Ranitidine HCl different dilutions were prepared. Five different dilutions of 5(µg\ml),10(µg\ml), 15(µg\ml), 20(µg\ml), 25(µg\ml), 30(µg\ml) was prepared from 1000 (µg\ml) standard stock solution.

Procedure: After preparation of standard and sample solutions, measurement of the absorbance of different dilutions 5 (µg\ml), 10(µg\ml), 15 (µg\ml), 20(µg\ml), 25(µg\ml) in 1cm cuvette by using UV visible Spectrophotometer.

Table No.04: Absorbance of Ranitidine HCL in 0.1N HCL at λ 310nm

Figure 02: Calibration graph of Ranitidine in 0.1 N HCL Solution

Table No.05: Absorbance of Ranitidine HCL in Distilled Water at λ 310nm

Figure 03: Calibration graph of Ranitidine HCL in Distilled water

• Solubility studies of the drug:

The Term Solubility is defined as the maximum amount of solute that can be dissolved in a given amount of solvent to form a homogenous system at the specified temperature and Specific

Procedure: To Prepare different solutions Water, HCL, Ethanol, and Chloroform. The drug material is added to the above solutions till Supersaturated Solution from the Mixture is shaken for 10 min till 2hours and after 24 to 72 hrs. Filter the mixture Take Filtrate and Give Absorbance to detect the Concentration of the Drug is Soluble in Different Solutions Pressure from a Saturated Solution.

Table No. 06: Determination of solubility of Ranitidine HCL in various solvent:

• Drug and Excipient Interaction Studies:

The raw material pure drug, a physical mixture of excipient, as well as polymer and formulation powder samples, were characterized by FTIR spectroscopy in the range of 4000– 400 cm- 1usingthe KBr pellet method. The different formulations of Excipients, drug and their physical mixtures were found to be stable under refrigerated conditions, and room temperature. As there were no changes in physical characteristics. Hence it was in referred that the selected excipients are compatible with the drug [7].

Figure 04: IR spectrum of the Floating Tablet of Ranitidine HCl. FT-IR spectra

Figure 05:IR spectrum of the Floating Tablet of Ranitidine HCl. With HPMCK4M

Figure 06: IR spectrum of the Floating tablet of Ranitidine HCl With Tara Gum

• Formulation Code:

Table No.: 07

The procedure of floating tablet of Ranitidine HCL

• • Firstly, all the elements have been weighed correctly on weighing balance and then pass through sieve No.40.
  • The drug HPMC and Carbapol 934, sodium bicarbonate, tartaric acid, and tara gum have been blending a mortar and pestle try to a get uniform pill blend.
  • In last talc and magnesium stearate have been blended with the so-received blend.
  • The compound turns into compressed into a round pill with the use of a rotator punch machine.
• Evaluation of Formulation:

• Pre-compression studies: Formulations prepared for compression were subjected to pre- compression parameters to study the flow properties of powders (repose angle, tapped density, bulk density, Hausner’s ratio, and compressibility index).

• The angle of Repose: To measure the repose angle of weighed powder, the method of the fixed funnel was used. The funnel was stationary with the help of a supporting stand such that the tip of the funnel remained 10cm above the horizontal surface. A circular dish of known radius (r) was positioned on a plane horizontal surface centered beneath the funnel tip, having sharp edges, and the diameter of its cone base was denoted as “D”. Powder was filled in the funnel and the funnel tip was obstructed with the thumb which was then immediately removed. The powder was permitted to fall through a funnel over a petridish till the excess powder slides down at the sides of the petridish. The vertical height (h) of the heap was obtained. The repose angle was calculated by given formula [10].

• • Bulk Density: Apparent bulk density was evaluated by torrential drug excipients mixture into a graduated cylinder and computing the weight and volume [7]

Whereas, Db depicts bulk density, M for mass, and Vb is bulk volume. The unit of bulk density is g/ml

• • Tapped Density: To find out the tapped density the graduated cylinder the powder sample. The initial powder volume was observed, marked at the graduated cylinder, and tapped onto the hard and smooth impervious surface until the mass or volume changes became constant. The tapped density was determined by the following formula [7].

Where as Dt depicts tapped density, M is for mass and Vt is for tapped volume.

• • • Carr’s Compressibility Index: It was calculated by importing previously received data of bulk and tapped density in to the following equation [7].

• • Hausner’s Ratio: It was calculated by inducing values of bulk and tapped density into the following formula:

• Post-compression Parameters:
  • Thickness: The thickness of the tablet is measured by using a screw gauge. It gives the changes in weight variation of tablets.
  • Hardness: The hardness of five tablets was determined using Pfizer & eureka hardness tester and average values were calculated
  • Friability: Friability is the measure of tablet strength. Roche friabilator was used for testing the friability using the following procedure.  Twenty tablets were weighed accurately and placed in the tumbling apparatus that revolve at 25 RPMs were weighed and the percentage loss in tablet. Dropping the tablet through a distance of six inches with each revolution. After 4 min, the tablet was weighed and the percentage loss in tablet weight was determined [12].

• Floating lag time: the lag time was carried out in a beaker containing 100ml of 0.1N HCL as a testing medium maintained at 370C.  the time required for the tablet to rise to the surface and float was determined as floating lag time.

• • Floating Time: floating time is the time, during which the tablet floated in 0.1N HCL dissolution medium (including floating lag time) on immersion in 0.1N HCL solution Ph (1.2) at 370C, the tablets floated, & remained buoyant without disintegration. Formulation containing HPMC K4M, Tara gum (FM-6) showed good FLT of 3min 30sec [13].
  • Swelling Index Study: Swelling index study was performed on all the batch (FM-1 to FM- 8). The result of the swelling index was shown. In the present study, a higher swelling index was found for tablet so f batch FM-6 containing a combination of HPMC K4M, and Tara Gum. Thus, the viscosity of the polymer had a major influence on the swelling process, matrix integrity, as well as floating capability, hence from the above results it can be concluded that a linear relationship exists between swelling processes [13].

• Content Uniformity: it is the amount present in each formulation for formulation (or tablets). Tablets from the formulation were taken and dropped in 100ml 0.1NHCL in a beaker. After 24 hours or when the drug is released completely the same sample was withdrawn (about1ml) and diluted to 10ml with 0.1N HCL and absorbance was taken at 314nm using a UV spectrometer. From the standard graph % drug release was calculated [14]
• In vitro Dissolution test: The rate of release of ranitidine from floating tablets was evaluated by the paddle method from united states pharmacopeia (USP) dissolution apparatus II (paddle method). dissolution test was performed using 0.1 N HCL (900ml) at 370C +_0.5 for 6 hours at 50rpm. An Aliquot equal to 5ml was taken at particular time intervals and the samples were substituted with renewed dissolution medium. The samples were filtered and diluted to a suitable concentration with 0. 1NHCL.These solutions’ absorbance was measured at 310 nm using a UV spectrophotometer. The cumulative percentage of the release of the drug was determined using the equation obtained from a standard curve [15]

RESULT:

Table No.08: Pre-Compression parameters of the blend.

Table No.09: Post-compression Parameters of Ranitidine HCl floating tablets.

Table No.10: Swelling index:

Table No.11: Cumulative Drug Release Profile of F1-F8