Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatriptan Succinate for Migraine Disorder

Research Article

Austin J Anal Pharm Chem. 2016; 3(2): 1063.

Formulation and Evaluation of Unidirection Bucco- Adhesive Tablet of Sumatriptan Succinate for Migraine Disorder

Champaneri AM*, Soniwala MM and Chavda JR

Department of Pharmaceutics, B. K. Mody Government Pharmacy College, Polytechnique Campus, Near Aji Dam, India

*Corresponding author: Ajay M Champaneri, Department of Pharmaceutics, B. K. Mody Government Pharmacy College, Polytechnique Campus, Near Aji Dam, India

Received: March 24, 2016; Accepted: May 03, 2016; Published: May 05, 2016

Abstract

The objective of this research work was to formulate and evaluate PEO WSR 301 bucco-adhesive tablet in combination with Carbopol 934p for controlled release of Sumatriptan Succinate. To bypass high hepatic first pass metabolism, unidirection bucco-adhesive tablet is selected dosage form for the experimental work. Initially preliminary trials were carried out for the selection of excipients and their relative quantity for incorporation in the dosage form. From the results, Polyethylene oxide-PEO WSR 301 (mucoadhesive polymer) and Carbopol 934p (control release) were selected as a suitable excipients for experimentation. Composition of the mucoadhesive tablet was optimized using 3² full factorial design where amount of PEO WSR 301 (X1) and amount of Carbopol 934p (X2) were taken as independent variables and mucoadhesive strength, Drug release at 6 hour and % swelling index taken as response variables. The formulations of design batches were characterized for post compression parameters like weight variation, hardness, thickness, friability, Drug content, swelling index, ex-vivo Mucoadhesive strength, and surface pH, drug release at 6 hr., ex-vivo residence time, and curve fitting analysis. The optimized formulation was obtained using Minitab software based on desirability value. Characterization of optimized batch was carried out by, ex-vivo permeation study.

From the results of meting point, DSC and FTIR study the drug and its compatibility with other excipients was confirmed. λmax of Sumatriptan Succinate was found to be 227 nm and linearity was 0.9995. Mucoadhesive strength and swelling index were in range of 0.25-0.43 N and 45-50% respectively. Drug release at 6hr. was in the range of 87-95%. The Bucco-adhesive of Sumatriptan succinate provides good concept to bypass the extensive hepatic first-pass metabolism. Formulated tablet using PEO-WSR 301 and Carbopol 934p showed good mucoadhesion, release profile, swelling index and permeation behavior. The Sumatriptan Succinate unidirection bucco-adhesive tablet is a promising approach for the effective treatment of disease as it provides control drug release in 6 hr.

Keyword: Unidirection buccal tablet; Sumatriptan succinate; Migraine; PEO WSR 301; Carbopol 934p

Introduction

Sumatriptan succinate is 1-[3-(2-dimethylaminoethyl)-1Hindol- 5-yl]-N-methyl-methane sulfonamide succinate [1,2]. It is a 5-HT1 receptor agonist used in the treatment of migraine. Migraine is a condition that affects approximately 10% of the adult population worldwide, yielding approximately 600 million people with about 28 million in the USA alone. In addition to headache, migraine can be associated with a variety of other symptoms, including diarrhea, cold extremities, facial pallor, nausea, vomiting, and sensitivity to external stimuli such as light, sound, or odor. Such migraines typically last for up to 24h, but can range from 4 to 72h and patients often experience migraine attacks one to two times per month. The oral formulation offers convenience and ease of use but produces unreliable blood levels and inconsistent response. Recurrence (rebound) occurs with these formulations. This common problem with recurrence is likely due to persistence of the original event with a time course exceeding the duration of action from the currently available formulations. This is particularly so because sumatriptan has a serum elimination half-life of only 2h and most of the active drug is eliminated within 4–6 h in the majority of patients. Thus, an optimal product would seek to provide the advantages of rapid, systemic administration of sumatriptan succinate. Buccal drug delivery system has the potential to fill an unmet need in migraine care by providing direct access to the systemic circulation through the internal jugular vein bypassing the first pass metabolism leading to high bioavailability. Other advantages are noninvasive administration, rapid-onset of action, convenient and easily accessible site, self-administrable, low enzymatic activity, suitability for drugs or excipients that mildly and reversibly damages or irritates the mucosa, painless administration, easy drug withdrawal, cheap and have superior patient compliance. In this work, it is designed to develop 9h bucco-adhesive tablets of sumatriptan succinate with the following objectives to avoid hepatic first pass metabolism, to reduce the frequency of administration, overcome the side effects, simplify the treatment regimen, and to obtain greater therapeutic efficacy to improve patient compliance.

Material and Method

Material

Sumatriptan succinate raw material was received as gift sample from Sun Pharmaceutical Limited, Ahmedabad, PEO WSR 301 from Lubrizol, Carbopol 934 p from ACS chemical, Ahmedabad, Lactose Monohydrate from Loba chemicals, Thane, Ethyl Cellulose from Loba chemicals, Mumbai, Magnesium Stearate from ASES, Jodhpur and Talc from Vikas pharma, Mumbai.

Method

Method of core tablet: The Sumatriptan succinate unidirection Bucco-adhesive tablet were prepared by direct compression method, the composition of various formulation was mentioned in Table 1 [3]. All the ingredient was individually passed through sieve no 60. The required quantities of mucoadhesive polymer were mix properly with other excipients. Prepared the core tablet in the tablet compression machine mini press-I (Karnavati, Ahmedabad). After prepared core tablet then using ethyl cellulose (backing layer) for the unidirectional design. Composition of the mucoadhesive tablet was optimized using 3² full factorial design where amount of PEO WSR 301 (X1) and amount of Carbopol 934p (X2) were taken as independent variables and mucoadhesive strength, Drug release at 6 hour and % swelling index taken as response variables. The formulations of design batches were characterized for post compression parameters like weight variation, hardness, thickness, friability, Drug content, swelling index, ex-vivo Mucoadhesive strength, surface pH, drug release at 6hr., ex-vivo residence time, and curve fitting analysis. The optimized formulation was obtained using Minitab software based on desirability value. Characterization of optimized batch was carried out by, ex-vivo permeation study.

Method of core-in-cup tablet: Total weight of the core tablet was 80mg, prepared by direct compression in 8 mm punch (excipient same as shown above). Resulted round shape flat core tablet is recompressed in 10mm round shape flat punch after adding ethyl cellulose (70mg) mixture at free three side around the tablet.

Identification of drug

Melting point method: Melting point of drug was determined by Capillary Method. Fine powder of Sumatriptan succinate was filled in glass capillary tube (previously sealed at one end), tube was placed in melting point apparatus and the temperature at which powder melted was noted.

IR Spectroscopy: FTIR studies were carried out to identify the drug [4]. Fourier Transform Infrared Spectroscopy studies were carried out by sample with dried potassium bromide and acquiring IR spectrum in the range of 400-4000 cm-1. The FT-IR spectrum of the obtained sample of the drug was compared with the standard FT-IR spectra of the pure drug.

DSC Study: Thermal behavior of drug was examined using thermal analyzer [4]. All accurately weighed samples (about 1mg) were placed in sealed aluminum pans before heating under nitrogen flow (20mL/min) at a scanning rate of 10 °C min-1 from 50 to 300 °C. An empty aluminum pan was used as reference.

Compatibility studies

FTIR spectroscopy: Compatibility must be established between the active ingredients and other excipients to produce a stable, efficacious, attractive and safe product. FTIR spectra of Sumatriptan succinate with different polymers and other excipients were recorded between 400 to 4000 cm–1 using FTIR spectrometer (Shimadzu).

Evaluation parameter

Pre Compression parameter of core powder blend

Bulk density: A bulk density is defined as the mass of powder divided by the volume [5,6,7]. A bulk density largely depends on the particle shape, as particles becomes more spherical in shape, bulk density is increase. In addition as granules size increase, bulk density decrease. Powder weighing 10 g was placed into 100 ml measuring cylinder. Volume occupied by the powder was noted without disturbing the cylinder and bulk density was calculated in gm/ml by the following equation.

Bulk density = Weight of powder / Bulk volume

Tapped density: Tapped density was achieved by mechanically tapping a measuring cylinder containing 20 tablet powders. After observing the initial volume, the cylinder was mechanically tapped and volume reading was taken until further volume changes were observed. The mechanical tapping was achieved by raising the cylinder and allowing it to drop under own weight a specific distance. Device that rotates the cylinder during tapping may be preferred to minimize any possible separation of the mass during tapping down. Cylinder dropping distance: 14 ± 2 mm at a normal rate of 300 drops /min. The final volume was recorded and the tap density was calculated by the following equation.

Tapped Density = Weight of powder / Tapped volume

Hausner’s ratio: The Hausner’s ratio is a number that is correlated to the flow ability of a powder or granular material.

Hausner’s Ratio = Tapped Density/Bulk density

Compressibility index (Carr’s index) [7]: Compressibility index of the drug was determined using the following formula

Carr’s Index (%) = [(Tapped Density-Bulk Density) x100]/ Tapped Density

Angle of repose: Angle of repose was determined by measuring the height, radius of the heap of the powder blend. A cut system funnel was fixed to a stand and bottom of the funnel was fixed at a height of 2cm from the plane. Powder blend was placed in funnel and allowed to flow freely and measured the height and radius of the heap.

tanθ=h/r

Where, h = height of heap

r = radius of heap

Post compression parameters of core tablet

Thickness: The thickness of buccal tablet was determined using digital micrometer screw gauge. Ten individual tablets from each batch were used and the average thickness was calculated.

Hardness: Hardness test was done for five tablets from each batch using hardness tester and average values was calculated. The hardness was measured in terms of kg/cm2.

Friability test: Friability is the measure of tablet strength. Roche type friabilator was used for testing the friability using the following procedure. Twenty tablets were weighed accurately and placed in the tumbling apparatus that revolves at 25rpm dropping the tablets through a distance of six inches with each revolution. After 4min, the tablets were weighed and the percentage loss was determined.

% Friability loss = [Initial weight − Final weight/Initial weight] X 100

Weight variation test: The USP-XXIX weight variation test was carried out by weighing 20 tablets individually, calculating the average weight, comparing the individual tablet weight to average weight. The tablet meet USP-XXIX test if no tablet differs by more than two times of percentage deviation USP-XXIX Standards for Weight Variation Test.

Content uniformity: Ten tablets from each batch was taken, crushed and mixed. From the mixture 5mg of drug equivalent of mixture was extracted thoroughly with 100mL of pH 6.8 phosphate buffer. The amount of drug present in each extract was determined using UV spectrophotometer at 271 nm. This procedure was repeated thrice and this average was calculated.

Ex-vivo mucoadhesion studies: The ex-vivo mucoadhesive strength was performed after application of the buccal tablet on freshly cut goat buccal mucosa. The fresh goat buccal mucosa was tied on the glass slide, and a mucoadhesive core side of each tablet was wetted with phosphate buffer pH 6.8 and adhered to the sheep buccal mucosa by applying a light force with a fingertip for 30 seconds. The modified physical balance was adjusted by keeping glass beaker on another side. Water was added by burette and weight of water needed to detach the tablet from goat buccal mucosa was recorded for the measure of mucoadhesive strength in grams [8,9] (Figure 1).