Formulation And Evaluation of Oral Disintegrating Tablet of Doxylamine Succinate

Tablet: Tablet is a solid dosage forms each containing a unit dose of one or more medicaments with or without suitable excipients. Tablets may be swallowed whole or being chewed. Some are dissolved or dispersed in water before administration. Some are put in oral cavity, where the active ingredient is liberated at a predetermined rate. Implants  or passeries may also be presented in form of tablet. Tablet may vary in shape and differ greatly in size and weight depending on the amount  of  medicinal  substance  and  the intended mode of administration. Tablets are usually solid, right circular cylinders, the end surfaces of which  are flat  or convex and the edges of which may be beveled. They may exist in other shapes like triangular, rectangular, etc. They may have lines or break- marks and may bear a symbol or other markings. They are sufficiently hard to withstand handling without crumbling or breaking1.  

Advantages of the Tablet dosages form

• Tablets are convenient to use and are an elegant dosage form.
• Objectionable odour and bitter taste can be masked by coating technique. .
• Tablets are generally inexpensive dosage form.
• Suitable for large scale production
• Greatest chemical and microbial stability over all oral dosage form.     

2. Material and Method:

Table No. 1 List of Material

UV Spectroscopic study

Preparation of standard stock solution in distilled water

The standard solution containing the drug was  prepared by dissolving 10 mg of DOXYLAMINE SUCCINATE was transferred into a 10 ml volumetric flask to which distilled water was added up to mark to produce 1000µg/ml53.

Preparation of stock solution in phosphate buffer (pH6.8)

The standard solution containing the drug was  prepared by dissolving 10 mg of DOXYLAMINE SUCCINATE was transferred into a 10 ml volumetric flask to which phosphate buffer pH 6.8 was added up to the mark to produce 1000 µg/ml53.

Determination of λ max in distilled water and phosphate buffer (pH6.8)

By appropriate dilution of standard drug solution with distilled water and phosphate buffer, a solution containing10μg/ml and 5µg/ml of DOXYLAMINE SUCCINATE was scanned within the range of 400 – 200 nm against distilled water and phosphate buffer pH 6.8 for the determination of maximum absorption for the drug in both the solvent.

Preparation of calibration curve

From the above stock solution,1ml (1000µg/ml)of solution was transferred into 10 ml of volumetric flask to prepare 100 µg/ml working standard, from which aliquots of 0.2, 0.4, 0.6, 0.8 and 1.0 ml were transferred and volume was make up with distilled water into 10 ml volumetric flask to obtain the final concentration range of 2, 4, 6, 8 and 10 µg / ml. The solution was separately analyzed. Same  procedure was followed for phosphate buffer  pH 6.854.

Drug characterization

Determination of melting point

The capillary tube was taken and its one end was sealed by heating it. The sealed capillary tube was filled with DOXYLAMINE SUCCINATE up to 1cm high. The tube was placed in melting point apparatus with a thermometer. The change in the sample was noted  on  a gradual increase in the temperature. The temperature at which the drug started melting and gets completely melted was noted55.

Solubility determination

The shake – flask method is  used to determine the solubility  of  DOXYLAMINE SUCCINATE in distilled water and phosphate buffer (pH6.8).The sample is which is in a Stopper flask or vial. The vials were sealed and stirred for 10 minutes. Then they were kept on an orbital flask shaker at 37oC for 24 hours. After solubilization of the drug, an extra amount of the drug was added to the vial. This process is repeated until saturation solubility of drugs indicated by the presence of an undissolved drug. Then the mixture is kept aside for 24 hours and centrifuged at 3000 rpm for 15 minutes. The supernatant was separated and diluted with the respective solvent. The concentration of the drug was analyzed at 260 nm and 264 nm using a UV- visible spectrophotometer55.

Drug – Excipients compatibility study: Preparation of TLC plate: Firstly silica gel-G slurry prepared by mixing silica gel- G with distilled water in mortar pestle and triturated continuously to make uniform slurry. The slurry was poured uniformly  on glass slide and allowed to dry plate in hot air oven at 120 o C. Preparation of sample: The blend of drug with excipients in the ratio of 1:1was dissolved in  water. A capillary tube was used to spot the sample on TLC plates. The diameter of each spot was limited to 0.3 cm. The compounds were spotted at 1 cm above from the bottom of the  plate.  Development  of  the  solvent system: The solvent system was prepared using ethanol: water (1:1) was used as mobile phase. The 100ml of small beaker was used and the solvent system was poured in it. The glass beaker was lined with filter paper for prostration with the solvent system for15-30 minutes56.

Stationary Phase – Precoated silica gel – G Mobile Phase–ethanol: water (1:1)

Development of thin layer plate: The previously spotted plates kept in mobile phase. Plates were developed in an ascending manner. When the solvent reached to the mark the plate was removed and the wet plates were dried.

Detection of spot: The iodine chamber was prepared and TLC plate was placed in a chamber. Therefore the plate was removed from chamber and spots was observed and calculate Rf value.   

Table. 2 Selection of excipients

The two factor three level design (32) was used for the formulation and optimization of orodispersible tablet of DOXILAMINE SUCCINATE and experimental trials are performed at all 9 possible formulations. In which the amount of sodium starch glycolate and cropovidone were selected as independent variables at three different level : low (-), medium (0), and high (+1) levels. The drug release and disintegration time used as a dependent variable (response).

Table No 3 formulation of oral disintegrating tablet of Doxilamine succinate

All ingredients were accurately weighed and passed through sieve no. 80 and collected in poly bags individually. Then DOXYLAMINE SUCCINATE drug was mixed with sodium starch  glycolate,  crosspovidone,  microcrystalline  cellulose,  and  sodium  saccharine  for specified time interval i.e. for 15 minutes. Then, magnesium stearate and talc was added. The compressed tablets were prepared by compressing the blend by rotary tablet compression machine (Aidmach) using 6mm round shaped dies and punches of B-toiling57.

EVALUATIONS PARAMETERS:    

Pre-compression parameters

Bulk density:

Bulk density was determined by pouring a 10 gm  of powder into a 100 ml measuring cylinder through funnel and measure the volume of powder58.

Bulk density = Mass of powder /  Poured volume of powder

Tapped Density:

10 gm of powder was weigh and transferred into the measuring cylinder. The measuring cylinder was then kept on a mechanical tapper apparatus and tapping of 100 times was done. The volume was occupied by the powdered bed was noted58.

Tapped density = Mass of powder / Tapped volume of powder

Angle of repose:

The powder flow property was determined by using the angle of repose. The height of the funnel was adjusted to 4cm above the working slab. The accurately weighed powdered blends were poured through the funnel until pile of powder touches the pipe of the funnel and the height of the powder and the diameter of the powder was noted and calculated. The powder flow property was determined by using angle of repose58.

tanθ=h/r

Where,

θ = angle of repose h = height

r = radius

Carr’s index: The Carr’s index was an indication of compressibility of a powder and calculated using the formula given below59.

Carr’s = bulk volume –tapped volume/bulk volume x 100

Hausner’s ratio:

It is found that the ratio of tapped density and bulk density. A value greater than 1.5 indicates poor flow, between 1.25 and 1.5 added glidant to improve flow and value less than1.25 indicated good flow59.

Hausner’s ratio =Tapped density / bulk density

EVALUATION OF PREPARED TABLET

Weight variation

20 tablets were selected randomly and weighed. The average weight was calculated. Not more than two of the individual weights should deviate from the average weight by more than percentage shown in the table and none deviates by more than twice that percentage. In for more than two tablets deviate from the range, retest 20 tablets were done and not more than 2 tablets should deviate from 40 tablets60.

Thickness

Tablet thickness was determined using Vernier caliper. The tablet was placed laterally between the jaws of Vernier caliper. Jaws were adjusted to just touch object to be measured. The reading was noted61.

Hardness

The tablet was placed on the holder. The “0” on Monsanto tester scale was set. The tablet was pressed. The range of Monsanto hardness tester was “0 to20” kg. The pressure was applied till the tablet breaks. The reading was noted62.

Friability

The tablets were weighed before placing in friability apparatus. 10 tablets were placed in the friability test apparatus. Switch was “ON” the mains. Tablets were taken out after 100 revolutions has completed. Re weighed the tablets after deducting62.

Wetting time

The tablet was placed at the center of two layers of absorbent paper fitted into a petri-dish.  After the paper was thoroughly wetted with distilled water excess water was completely drained out of the dish. The time required for the water to diffuse from the wetted absorbent paper throughout the entire tablet was then recorded using a stop watch63

Water absorption ratio

A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. A tablet was put on the tissue paper and allowed to completely wet. The wetted tablets were reweighed. Water absorption ration, R was determined using following equation64.

R=100×Wa-Wb/Wa

Where,

Wa = Weight of tablet after water absorption

Wb = Weight of tablet before water absorption    

Disintegration Time

One tablet was introduced into each tube and added a disc to each tube. The assembly was suspended in the beaker containing purified water. The apparatus was operated until the tablet completely disintegrates. The time taken was noted for the complete disintegration of    the   tablet   without   any   remitants.   The   assembly   was   removed   from   water6

3. Result and Discussion

Pre formulation studies

Drug characterization

Melting point: Melting point of Doxylamine Succinate was determined by capillary method. The melting point of Doxylamine Succinate was found to be 103?C which was similar as reported [66].

Table. 4 Melting Point of Doxylamine Succinate

Determination of wave length using UV spectrophotometric analysis:

The maximum wavelength of Doxylamine Succinate was found to be 260 nm. This was found to be similar as required wavelength [66]. The UV spectrum of Doxylamine Succinate drug is shown in the figure 7.2.

Figure 1: Spectrum of Doxylamine Succinate by UV Spectroscopy

Preparation of calibration curves:

The calibration curves of Doxylamine Succinate in various solvents e.g. Distilled water, phosphate buffer pH 6.8 were prepared and shown below [67]:

Table 5: Absorbance data of Doxylamine Succinate in distilled water for preparation of

Figure 2: Calibration curve of Doxylamine Succinate in phosphate buffer pH 6.8

Determination of solubility of Doxylamine Succinate in various medium:

The solubility of Doxylamine Succinate in various mediums was studied and the results of study were shown in below table:

Table- 6: Solubility data of Doxylamine Succinate in different mediums

The above solubility data have satisfactory results [68].

Drug- excipient interaction study:

The drug (Doxylamine Succinate) was found to be compatible with various excipients which were selected for formulation of oral disintegrating tablet. The compatibility was assessed by TLC and the retention factors of all ratios found similar [69].

Table 7: Data of drug-excipient interaction study

Formulation and Development

Pre Compression Characterization:

Bulk density, Tapped density, Carr’s index, Hausner’s ratio, Angle of repose

The bulk density, tapped density, Carr’s index, Hausner’s ratio and angle of repose of drug excipient mixture were performed and shown in table 7.7. All the results show that mixture possess a good flow property [70].

Table  8: Pre Compression Characterization:

Determination of Physicochemical Properties of Oral Disintegrating Tablet

The various physicochemical properties were evaluated like thickness, hardness, weight variation, friability, drug content, disintegration time, wetting time and the results of the study were shown in below table:

Table  9 Absorbance data of Doxylamine Succinate in distilled water for preparation of calibration curve at 260 nm

Figure  3: Calibration curve of Doxylamine Succinate in phosphate buffer pH 6.8

Determination of solubility of Doxylamine Succinate in various medium:

The solubility of Doxylamine Succinate in various mediums was studied and the results of study were shown in below table:

Table 10 Hardness, Thickness, Percentage Friability and Average weight of Batch F1-F9

Table 11 Disintegration Time, Drug Content Uniformity, Water Absorption Ratio and Wetting Time of Batch F1-F9

In-vitro drug release study for Oral Disintegrating tablet:

The percentage drug release from formulations F1 to F9 was found to be more than 90 % drug within 30 minutes. Based on below results, formulation F9 was selected as best formulation.

Figure 4  Percentage drug release data of F1 to F9 formulation of Oral  Disintegrating tablets

Stability study for Oral Disintegrating tablet

The stability studies of prepared tablets were performed after 1 month and 2 month and found satisfactory results.