INTRODUCTION:

Ondansetron is a serotonin 5-HT₃ receptor antagonist used mainly as an antiemetic (to treat nausea and vomiting), often following chemotherapy. It affects both peripheral and central nerves. Ondansetron reduces the activity of the vagus nerve, which deactivates the vomiting center, and also blocks serotonin receptors in the chemoreceptor trigger zone. Here quick action is necessary to prevent nausea and vomiting¹.

It is important to formulate it as per novel drug delivery system. The advances in novel drug delivery are to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for ease of administration and to achieve better patient compliance. One such approach is oral disintegrating tablets (ODTs)².

A novel oral dosage form known as Oral Disintegrating Tablets (ODTs) which disintegrate rapidly in saliva, usually in a matter of seconds, without the need to take water. Drug dissolution and absorption as well as onset of clinical effect and drug bioavailability may be significantly greater than those observed from conventional dosage forms. ODTs with good taste and flavor increase the acceptability of bitter drugs by various groups of population³.

The major advantage of the Oral Disintegrating Tablets (ODTs) formulation is that it combines the advantages of both liquid and conventional tablet formulations, and also offering advantages over both traditional dosage forms. It provides the convenience of a tablet formulation, and also allowing the ease of swallowing provided by the liquid formulation. Some novel Oral Disintegrating Tablets (ODTs) technology allow high drug loading, have an acceptable taste, offer a pleasant mouth felling, leaving minimal residue in the mouth after oral administration. It provides good stability, accurate dosing, easy manufacturing^4,5.

The basic approach in development of Fast Dissolving Tablets (FDT) is the use of super disintegrants like cross linked carboxymethyl cellulose(croscarmellose), sodium starch glycolate (primogel, explotab), polyvinylpyrollidone (polyplasdone) etc, which provide instantaneous disintegration of tablet after putting on tongue, their by release the drug in saliva. The bioavailability of some drugs may be increased due to absorption of drug in oral cavity and also due to pre gastric absorption of saliva containing dispersed drugs that pass down into the stomach. More ever, the amount of drug that is subjected to first pass metabolism is reduced as compared to standard tablet⁶.

The aim of the present study was to prepare quick release tablets of Ondansetron using superdisintegrants such as crospovidone, croscarmellose sodium, sodium starch glycolate, kyron T-314 and combination of crospovidone with croscarmellose sodium, crospovidone with sodium starch glycolate and crospovidone with kyron T-314 in different concentration.

MATERIALS AND METHODS:

Ondansetron hydrochloride was purchased from Natco Pharma Ltd, Hyderabad, India. Polyethylene glycol-6000 and hydroxy propyl methyl cellulose were purchased from Dow chemical Inc., Mumbai, India. Crospovidone and croscarmellose sodium were purchased from ISP Chemical Inc., Hyderabad, India. Sodium starch glcolate and mannitol were purchased from Roquette Chemicals, Mumbai, India. Kyron T – 314 and stearic acid were purchased from M/S Sterinerie Dubois Fils., Pune, India. Micro crystalline cellulose was purchased from Bramhar Cellulose Products Ltd., Tamilnadu, India. Colloidal silicon dioxide was purchased from Bayer Chemicals, Pune, India. Aspartame was purchased from Nutrasweet Chemicals, Vadodara, India. Vannila was purchased from Merck, Hyderabad.

Methods:

Formulation Development:

Formulation of Ondansetron Hydrochloride Orodispersible tablets by direct compression of the coated solid dispersion involves use of Polyethylene glycol-6000 as a carrier, Hydroxy propyl methyl cellulose as a coating agent and mannitol and microcrystalline cellulose as diluent, Crospovidone, Croscarmellose Sodium, Sodium starch glycolate, KyronT-314 (Polacrillin pottasium) and their combinations as superdisintegrants, colloidal silicone dioxide as glidant and stearic acid as lubricant, aspartame as sweetener, and vannila as flavouring agent. To select best superdisintegrant for this formulation and its effective concentration various batches were taken at different concentration range from 3 to 5 % w/w for each superdisintegrant and their combinations^{7, 8}.

Optimaization of formulation:

Development of formulation in the present study was mainly based on the type of carriers, for solid dispersion preparation, and polymers for coating of the formed solid dispersion granules.

Initially formulations were prepared using the carriers namely Poloxamer and PEG 6000 of which PEG 6000 gave better taste masking and disintegration of the solid dispersion granules. These formed granules were coated with HPMC and HPC, where HPMC favoured better taste masking. Hence, PEG 6000 was selected as the solid dispersion carrier and HPMC was chosen as the taste masking coating polymer.

Then different ratios of ondansetron Hydrochloride: Polyethylene glycol like 1:1, 1:2 and 1:3 were prepared to taste mask the bitterness of the drug and the coating carrier like HPMC in the ratios of 0.5%, 1%, 1.5% were employed for better taste masking of the drug. The bitterness of the drug was masked at 1:2 ratio of drug: PEG and 1% HPMC were chosen for the tablet preparation. So, in the present study attempts were made to get better taste masking and good physical and analytical (release profile) parameters of the tablets.

Preparation of Solid Dispersion (Coated granules):

Weighed quantities of Drug (Ondansetron Hydrochloride) and sweetener (Aspartame 0.5%) were taken and mixed uniformly. PEG-6000 was weighed and was melted in a clean petridish, until a clear solution was formed. To the above preparation drug mixture was added slowly to the melted polymer. This mixture formed was rapidly cooled which resulted in a hard mass, which was then sieved through number 40 mesh. In another beaker 1% w/v solution of HPMC was prepared with water. This solution was added drop wise to the above prepared drug granules, where a soft mass was formed and which on sieving through number 33 mesh gave coated granules.

Compression of Coated Granules:

Excipients like Crospovidone, Sodium starch glycolate, Kyron T-314, MCC, mannitol, aspartame and vanilla were weighed and measured accurately and added to the taste masked granules. Stearic acid and colloidal silica which were previously passed through sieve no. 33 and mixed well were added to this well blended mixture. This mixture was compressed into tablets using 7mm tablet punching machine⁹. The formulations of different batches were given in table 1 and 2.

Table 1. Formula of Ondansetron HCl Oral Disintegrating Tablets Prepared Using Different Superdisintegrants

Ingredient	F₁	F₂	F₃	F₄	F₅	F₆	F₇	F₈	F₉	F₁₀	F₁₁	F₁₂
DPC	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568
CP	3	4	5	-	-	-	-	-	-	-
CCS	-	-	-	3	4	5	-	-	-	-
SSG	-	-	-	-	-	-	3	4	5	-	-	-
K T – 314		-	-	-	-	-	-	-	-	3	4	5
Mannitol	38	38	38	38	38	38	38	38	38	38	38	38
MCC		38.932	37.932	36.932	38.932	37.932	36.932	38.932	37.932	36.932	36.932	36.932
earic acid	1	1	1	1	1	1	1	1	1	1	1	1
Colloidal Silica	1	1	1	1	1	1	1	1	1	1	1	1
Aspartame	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5
Vannila	1	1	1	1	1	1	1	1	1	1	1	1

*DPC – Drug Polymer Complex, CP – Crosspovidone, CCS – Croscarmellose Sodium, SSG – Sodium Starch Glycolate

* All the amounts given in above table are in milligrams.

Table 2. Formula of Ondansetron HCl Oral Disintegrating Tablets Prepared with Combination of Superdisintegrants

Ingredient	F₁₃	F₁₄	F₁₅	F₁₆	F₁₇	F₁₈	F₁₉	F₂₀	F₂₁
DPC	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568	16.568
CP+CCS	3(1:1)	4.5(2:1)	4.5(1:2)	-	-	-	-	-	-
CP+SSG	-	-	-	3(1:1)	4.5(2:1)	4.5(1:2)	-	-	-
CP+KT-314	-	-	-	-	-	-	3(1:1)	4.5(2:1)	4.5(1:2)
Mannitol	38	38	38	38	38	38	38	38	38
MCC	38.932	37.432	37.432	38.932	37.432	37.432	38.932	37.932	37.932
stearic acid	1	1	1	1	1	1	1	1	1
Colloidal Silica	1	1	1	1	1	1	1	1	1
Aspartame	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5
Vannila	1	1	1	1	1	1	1	1	1

*DPC – Drug Polymer Complex, CP – Crosspovidone, CCS – Croscarmellose Sodium, SSG – Sodium Starch Glycolate

* All the amounts given in above table are in milligrams.

Evaluation of Oral Disintegrating Tablets of Ondansetron Hydrochloride:

Fourier Transform Infrared (FTIR) Spectroscopy:

A Fourier Transform – Infra Red spectrophotometer was used to study the non-thermal analysis of drug-excipient compatibility. The spectrum of each sample was recorded over the 4000-400 cm^-1.Pure drug of Ondansetron hydrochloride. Ondansetron hydrochloride solid dispersion and Ondansetron hydrochloride with excipients compatibility studies were performed¹⁰.

Pre-Compression Parameters:

Flow Properties:

Angle of Repose:

This was determined by using funnel method. Powder was poured from a funnel that can be raised vertically until a maximum cone height (h), was obtained. Diameter of heap, (D), was measured. The angle of repose (è) was calculated by the following equations,

tan θ = h / r

θ = tan ^-1 (h / r)

Where,

θ = Angle of repose,

h = height of the pile (cm) and

r = radius of the pile.

Bulk Density:

The sample under test was screened through sieve # 18, the sample equivalent to 25 g was accurately weighed and filled in a 100 ml graduated cylinder, the powder was leveled, and the untapped volume, V0 was noted. The bulk density was calculated in g/cm³ by the following equation,

D_b= M / V₀

Where,

M= Mass of powder,

V₀= Bulk volume of the powder,

D_b = Bulk Density¹¹.

Tapped Density:

The sample under test was screened through sieve # 18 and the weight of sample equivalent to 25 g was filled in 100 ml graduated cylinder. The mechanical tapping of the cylinder was carried out using tapped density tester at a nominal rate of 300 drops per min for 500 times initially and the tapped volume V₀was noted. Tapping was proceeded further for an additional tapping 750 times and tapped volume V_b was noted. The difference between two tapping volume must be less than 2%. V_b was considered as a tapped volume V_f. The tapped density was calculated in g/ cm³ by the following equation.

Dt = M / V_f

Where,

M = Mass of powder,

Vt = Tapped volume of the powder,

Dt= Tapped Density¹².

Hausner Ratio:

The ratio of Tapped density and bulk density gives the Hausner ratio and it was calculated using the following equation,

HR= D_t / D_b

Where,

D_t = Tapped density of the powder,

D_b = Bulk density of the powder¹³.

Compressibility Index:

The bulk density and tapped density was measured and compressibility index was calculated by the following equation,

IC = D_t - D_b / D_t

Where,

D_t = Tapped density of the powder,

D_b =Bulk density of the powder¹⁴.

Post Compression Parameters:

Weight variation:

Twenty tablets were randomly selected from each batch and individually weighed. The average weight and standard deviation three batches were calculated. It passes the test for weight variation test if not more than two of the individual tablet weights deviate frm the average weight by more than the allowed percentage deviation and none deviate by more than twice the percentage shown. It was calculated on an electronic weighing balance.

Thickness Test:

The rule of physical dimension of the tablets such as sizes and thickness is necessary for consumer acceptance and maintain tablet uniformity. The dimensional specifications were measured by using screw gauge. The thickness of the tablet is mostly related to the tablet hardness can be used as initial control parameter.

Hardness Test:

The hardness of tablets was measured by using Monsanto hardness tester. The results were complies with Indian Pharmacopoeial specification¹⁵.

Friability Test:

Twenty tablets were weighed and subjected to drum of friability test apparatus. The drum rotated at a speed of 25 rpm. The friabilator was operated for 4 minutes and reweighed the tablets. % loss(F) was calculated by the following formula.

F =100 (W0-W)/W₀

Where

W₀ = Initial weight,

W = Final weight¹⁶.

Drug Content Uniformity:

The content uniformity test is used to ensure that every tablet contains the amount of drug substance intended with little variation among tablets within a batch.

Five tablets were selected randomly and average weight was calculated. Tablets were crushed in a mortar and accurately weighed and the amount of average tablet was taken from the crushed blend. Then, the samples were transferred to three 100 ml volumetric flasks and were diluted up to the mark 0.1N HCl solution. The content was shaken periodically and kept for 24 hours for dissolution of drug completely. The mixtures were filtered and appropriate dilutions were made. The drug content in each tablet was estimated at lmax 310.0 nm against blank reference and reported.

Disintegration Time:

Disintegration time is the time taken by the tablet to break into smaller particles. The disintegration test is carried out in an apparatus containing a basket rack assembly with six glass tubes which consists of a 10 mesh sieve. The basket is raised and lowered 28-32 times per minute in the medium of 900 ml of purified water which is maintained at 37±2^oC. Six tablets were placed in each of the tubes and the time required for complete passage of tablet fragments through the sieve (number 10) was considered as the disintegration time of the tablet. The time for disintegration of oral dissolving tablets is generally <1min and actual disintegration time that patience can experience ranges from 5 to 30 secs.

Wetting Time:

Wetting time of dosage form is related with the contact angle. Wetting time of the mouth dissolving tablets is another important parameter, which needs to be assessed to give an insight into the disintegration properties of the tablets; a lower wetting time implies a quicker disintegration of the tablet. The wetting time of the tablet can be measured using a simple procedure.

Five circular tissue papers of 10 cm diameter were placed in a petri dish with a 10 cm diameter. 10 mL of water was added to petri dish and 2 drops of eosin red dye was added. A tablet was carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the tablet was noted as wetting time.

In-vitro Dispersion Time:

Tablet was added to 10ml of distilled water at 37±0.5⁰C. Time required for complete dispersion of a tablet was measured.

Water Absorption Ratio (R):

The weight of the tablet before keeping in the petri dish was noted (W_b) using Shimadzu digital balance. The wetted tablet from the petri dish was taken and reweighed (W_a) using the same. The Water absorption ratio, R, was determined according to the following equation:

R = 100 (Wa - W_b) / W_b

Where

W_b and W_a are the weight before and after water absorption respectively¹⁷.

Calibration Curve of Ondansetron Hydrochloride:

124.7mg of Ondansetron hydrochloride equivalent to 100mg of Ondansetron was accurately weighed and dissolved in Methanol in 100 mL volumetric flask. The volume was made up to 100 mL with Methanol to obtain a stock solution of concentration 1mg/mL. This solution was serially diluted with Methanol to get solutions of concentrations ranging from 2mg/mL to 15mg/mL. The absorbance of these solutions were measured at 246 nm using Methanol as blank. Standard plot was plotted.

Dissolution Studies:

Dissolution is a process by which the disintegrated solid solute enters the solution. The test determines the time required for a definite percentage of the drug in a tablet to dissolve under specified conditions.

In vitro drug release studies were carried out by using USP XXIII Dissolution Apparatus II (Paddle Type) at 50 rpm. The drug release profile was studied in 900 ml of 0.1N HCl maintained at 37 ± 0.5^oC. Aliquots of 5 ml of dissolution medium were withdrawn at specific time intervals (2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 25 and 30 minutes) filtered and the amount of drug released was determined by UV-Visible spectrophotometer. 10 mL of fresh buffer sample was replaced as soon as the drug samples were withdrawn. Samples withdrawn were analyzed for the percentage of drug release¹⁸.

RESULTS AND DISCUSSIONS:

Different formulations of Ondansetron hydrochloride oral disintegrating tablets were prepared using different superdisintegrants and mixtures of superdisintegrants. FTIT results showed no interactions between drug and excipients and Ondansetron hydrochloride solid dispersion (Figure 1- 3).

The precompression blend of Ondansetron hydrochloride solid dispersion with superdisintegrants and combination of superdisintegrants were characterized with respect to angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio (table 3 and 4). Angle of repose was less than 30, and in F14 batch it was 24.23±0.06. Bulk density values were between 0.57±0.049 to 0.66±0.059 and in F14 batch it was 0.58±0.034. Tapped density values were between 0.64±0.035 to0.69±0.047 and in F14 batch it was 0.69±0.047. Compressibilty index (%) were between 9.09 to 12.12 and in F14 batch it was 10.29. Hausner's ratio values were between 1.10 to1.13 and in F14 batch it was 1.10. All results showed powder has good flow properties.

All the formulations were evaluated for uniformity of weight, hardness, thickness and friability and the results are shown in table 5 and 6. The average tablet weight of all the formulations was found to be between 99.15 to 100.25 and in F14 batch it was 100.09. The average hardness of tablets of all the formulations was found to be between 3.10±0.05 to 3.45±0.15 and in F14 batch it was 3.41±0.2. The thickness of tablets of all the formulations was found to be between 2.43±0.01 to 2.47±0.03 and in F14 batch it was 2.46±0.01. The friability of tablets of all the formulations was found to be between 0.21±0.07 to 0.35±0.04 and in F14 batch it was 0.21±0.07.

All the formulations were evaluated for the drug content estimation in a pooled sample of tablets using the procedure described in methodology section. The drug content value for all the formulations are in the range of 99.09 to 101.87 % and in F14 batches it was 101.07. It was confirmed that all formulations content required percentage of Ondansetron hydrochloride. Wetting is closely related to inner structure of tablets. The wetting time in different formulations vary according to the ability of superdisintegrants for swelling and capacity of absorption of water. The wetting times of the formulations were in the range 22 to 36 seconds and in F14 batches it was 22±0.97. Water absorption ratio ranged from 49.23 to 64.41%. Water absorption ratio ‘R’ increased with an increase in superdisintegrants concentrations from 4-10%. The increase in ‘R’ might be due to increase in uptake of water for Crospovidone and crosscarmilose sodium at higher concentrations. Crosspovidone and croscarmellose sodium perform their disintegrating action by wicking through capillary action and fibrous structure, respectively with minimum gelling. The relative ability of the various disintegrants to wick water into the tablets was studied. Tablets containing combination of crospovidone and crosscarmellose (F14) sodium quickly wicks water and were hydrated. In F14 batches it was 64.41.

The most important parameter that needs to be optimized in the development of oro-dispersible tablets is the disintegration time of tablets. The average in vitro disintegration time for all the formulations lies within the range of 10 to 32 seconds fulfilling the official requirements (< 3 minutes) for orally disintegrating tablets.

Formulations containing crospovidone as superdisintegrant F1, F2, F3 in concentrations 3%, 4% and 5% respectively showed disintegration times at 21, 16 and 12 seconds.

Formulations containing croscarmellose sodium as superdisintegrant F4, F5, F6 in concentrations 3%, 4% and 5% respectively showed disintegration times at 23, 19 and 17 seconds.

Formulations containing sodium starch gylcolate as superdisintegrant F7, F8, F9 in concentrations 3%, 4 % and 5% respectively and showed disintegration times at 24, 21 and18 seconds.

Formulations containing kyronT-314 as superdisintegrant F10, F11, F12 in concentrations 3%, 4% and 5% respectively showed disintegration times 32, 30 and 24 seconds.

Formulations containing combination of crospovidone and croscarmellose sodium as superdisintegrant F13, F14, F15 in 1:1, 2:1 and 1:2 ratios respectively showed disintegration times at 14, 10 and 12 seconds.

Formulations containing crospovidone and sodium starch glycolate as superdisintegrant F16, F17, F18 in 1:1, 2:1 and 1:2 ratios respectively showed disintegration times at 18, 15 and 16 seconds.

Formulations containing crospovidone and kyron T-314 as superdisintegrant F19, F20, F21 in 1:1, 2:1 and 1:2 ratios respectively and showed disintegration times at 21, 17 and 19 seconds.

The faster disintegration of tablets containing combination of crospovidone and croscarmellose sodium in 2:1 ratio (F14) may be attributed to its rapid capillary activity and pronounced hydration with little tendency to gel formation. Thus, the results suggest that the disintegration time can be decreased by using wicking type of disintegrants. Hence the formulation F₁₄ showed less disintegration time when compared to all the formulations. The in-vitro dispersion time of all the formulations were in the range 7 to 24 seconds. In the present study, all the formulations dispersion in ≤ 30 sec fulfilling the official requirement (<3 min) for dispersible tablets.

The percentage drug content, wetting time, water absorption ratio, in-vitro disintegration time and in-vitro dispersion time values of formulations from F1to F12 are tabulated in table 7 and formulations from F13 to F 21 are tabulated in table 8. All formulations complies pharmacopeial standard.

The in-vitro dissolution study of Ondansetron hydrochloride tablet is tested by using 0.1N HCl as buffer. The in vitro drug release study of oro-dispersible tablets from each batch (F1 to F21) was carried out by using 0.1N HCl for 30 mins. The samples were withdrawn at specified time intervals and analyzed by UV-Visible Spectrophotometer. Percentage drug release was calculated on the basis of mean amount of Ondansetron hydrochloride present in the respective formulation. The percentage of drug release of Orodispersible formulations of Ondansetron hydrochloride was plotted against time to obtain drug release profiles.

From the in-vitro dissolution data, it was found that the formulations containing crospovidone (F₁, F₂ and F₃) showed 99.9%, 98.22 %and 99.92% drug release respectively given in the figure 4.

Due to the highly porous nature and high crosslink density, crospovidone shows the superdisintegrant property by both wicking and swelling action, which aids in faster disintegration of the tablet. Due to the combined action, tablets made with crospovidone showed faster dissolution than the other superdisintegrants and 5% showed 99.92% dissolution in 12 minutes it indicates that crospovidone was effective at concentration 5%, by decreasing concentration of crospovidone showed increasing disintegration and dissolution time.

From the in vitro dissolution data, it was found that the drug release study from formulations containing croscarmellose sodium (F4, F5, F6) showed 99.89, 99.53 and 99.37 drug release respectively given in the figure 5.

Tablets containing croscarmellose sodium (at 3%, 4%, 5% conc) achieved more than 99.89% dissolution approximately in 18 min and met the requirements of in- vitro dissolution.

Croscarmellose sodium at a concentration of 5% showed 99.53% drug release in 14 minutes, here also decreasing concentration of croscarmellose sodium showed increasing dissolution time.

From the in vitro dissolution data, it was found that the formulations containing sodium starch glycolate (F7, F8, F9) showed 99.59, 99.27 and 99.92 drug release respectively given in the figure 6.

Tablets containing sodium starch glycolate (at 3%, 4%, 5% conc) achieved more than 99.59% dissolution approximately in 18 min and met the requirements of in-vitro dissolution.

Sodium starch glycolate at a concentration of 5% showed 99.92% drug release in 14 minutes, here also decreasing concentration of Sodium starch glycolate showed increasing dissolution time.

From the in vitro dissolution data, it was found that the drug release study from formulations containing Kyron T-314 (F10, F11, F12) showed 99.73, 99.72 and 99.81 drug release respectively given in the figure 7.

Tablets containing Kyron T-314 (at 3%, 4%, 5% conc) achieved more than 99.73% dissolution in 20 min and met the requirements of in vitro dissolution.

Kyron T-314 at a concentration of 5% showed 99.81% drug release in 16 minutes, and at concentration of 3% showed 99.73% drug release in 20 minutes it indicates that decreasing concentration of superdisintigrant Kyron T-314 showed increasing dissolution time.

From the in vitro dissolution data, it was found that the formulations containing combination of crospovidone and croscarmellose sodium (F13, F14 and F15) showed 99.22%, 100.09 %and 98.99% drug release respectively given in the figure 8.

Due to the combined action of CP and CCS in 2:1 (3% CP+ 1.5% CCS) showed faster dissolution than the other combination of superdisintegrants and also showed 100.09 % dissolution within 8 minutes (F14).

From the in-vitro dissolution data, it was found that the formulations containing combination of crospovidone and sodium starch glycolate (F16, F17 and F18) showed 99.49%, 99.57 %and 99.82% drug release respectively given in the figure 9.

Due to the combined action of CP and SSG in 2:1(3% CP+ 1.5% SSG) showed 99.57% drug release with in 10 min.

From the in-vitro dissolution data, it was found that the formulations containing combination of crospovidone and kyron T-314 (F19, F20 and F21) showed 99.84%, 99.96 %and 99.32% drug release respectively given in the figure 10.

Hence based on dissolution data analysis of 21 formulations, F14 formulation showed fast release of drug (100.09 %) at 8 mins and it was confirmed as optimized formulation.

Figure 1. FTIR Report of Ondansetron HCl Active Pharmaceutical Ingredient

Figure 2. FTIR report of Ondansetron HCl Solid Dispersion

Figure 3. FTIR Report of Ondansetron HCl With Excipients

Table 3. Evaluation of Pre-compression Parameters of Ondansetron HCl Oral Disintegrating Tablets Prepared With Different Types of Superdisintegrants

Formulation code	*Angle of Repose (ө)**	*Bulk Density (g/cc)**	*Tapped Density(g/cc)**	Compressibilty index (%)	Hausner's ratio
F₁	27.78±0.04	0.59±0.067	0.67±0.075	11.94	1.13
F₂	29.72±0.04	0.58±0.034	0.65±0.084	10.76	1.12
F₃	28.73±0.05	0.60±0.057	0.66±0.046	9.09	1.10
F₄	26.57±0.06	0.57±0.056	0.64±0.076	10.93	1.12
F₅	28.43±0.04	0.58±0.067	0.66±0.057	12.12	1.13
F₆	29.85±0.07	0.57±0.087	0.64±0.035	10.93	1.12
F₇	27.14±0.07	0.61±0.046	0.68±0.057	10.29	1.11
F₈	28.68±0.05	0.58±0.048	0.64±0.068	10.82	1.10
F₉	26.23±0.06	0.62±0.047	0.69±0.047	10.14	1.11
F₁₀	27.14±0.07	0.60±0.023	0.67±0.086	10.44	1.11
F₁₁	28.47±0.05	0.62±0.063	0.65±0.048	11.82	1.12
F₁₂	27.39±0.06	0.66±0.059	0.66±0.059	11.29	1.13

*Mean ± S.D, n = 3

Table 4. Evaluation of Pre-compression Parameters of Ondansetron HCl Oral Disintegrating Tablets Prepared with Combination of Superdisintegrants

Formulation code	*Angle of repose (ө)**	*Bulk density (g/cc)**	*Tapped density (g/cc)**	Compressibilty index (%)	Hausner’s ratio
F₁₃	27.14±0.07	0.61±0.046	0.68±0.057	10.34	1.11
F₁₄	24.23±0.06	0.58±0.034	0.69±0.047	10.29	1.10
F₁₅	27.14±0.07	0.60±0.057	0.67±0.086	10.44	1.11
F₁₆	28.47±0.05	0.58±0.048	0.66±0.059	11.12	1.12
F₁₇	28.82±0.06	0.59±0.046	0.64±0.038	10.82	1.11
F₁₈	29.54±0.05	0.60±0.061	0.68±0.072	10.36	1.12
F₁₉	27.67±0.07	0.62±0.048	0.67±0.049	10.79	1.13
F₂₀	28.59±0.04	0.57±0.049	0.64±0.052	10.98	1.12
F₂₁	29.23±0.06	0.59±0.063	0.67±0.058	11.27	1.11

*Mean ± S.D, n = 3

Table 5. Evaluation of Post Compression Parameters of Formulations using Superdisintegrants

Formulation code	Weight variation^a (mg)	Hardness^a (kg/cm²)	Thickness^a (mm)	Friability^b (%)
F₁	99.75	3.22±0.1	2.46±0.02	0.26±0.03
F₂	99.15	3.18±0.2	2.47± 0.01	0.35±0.04
F₃	100.08	3.10±0.05	2.44±0.04	0.37±0.06
F₄	99.70	3.30±0.15	2.46±0.03	0.29±0.04
F₅	100.25	3.28±0.05	2.45±0.02	0.32±0.02
F₆	99.78	3.25±0.1	2.46±0.02	0.35±0.03
F₇	100.48	3.45±0.15	2.43±0.01	0.25±0.06
F₈	99.50	3.41±0.2	2.43±0.01	0.21±0.07
F₉	100.00	3.35±0.15	2.44±0.03	0.34±0.05
F₁₀	99.77	3.12±0.1	2.46±0.01	0.34±0.07
F₁₁	99.80	3.20±0.2	2.44±0.02	0.25±0.02
F₁₂	99.95	3.40±0.05	2.43±0.01	0.33±0.07

a: Mean ± S.D., n = 10 tablets and b: Mean ± S.D., n = 6 tablets

Table 6. Evaluation of Post Compression Parameters of Formulations using Combinations of Superdisintegrants

Formulation code	Weight variation^a (mg)	Hardness^a(kg/cm²)	Thickness^a (mm)	Friability^b (%)
F₁₃	99.75	3.45±0.15	2.43±0.02	0.25±0.06
F₁₄	100.09	3.41±0.2	2.46±0.01	0.21±0.07
F₁₅	99.89	3.35±0.15	2.44±0.03	0.29±0.05
F₁₆	99.85	3.28±0.05	2.46±0.02	0.32±0.02
F₁₇	100.2	3.38±0.2	2.45±0.02	0.33±0.04
F₁₈	99.70	3.45±0.15	2.47±0.03	0.31±0.06
F₁₉	99.88	3.29±0.05	2.44±0.02	0.30±0.06
F₂₀	99.25	3.42±0.2	2.43±0.01	0.28±0.07
F₂₁	99.15	3.35±0.15	2.47±0.01	0.30±0.05

a: Mean ± S.D., n = 10 tablets and b: Mean ± S.D., n = 6 tablets

Table 7. Evaluation of Formulations of Ondansetron HCl using Superdisintegrants

Formulation code	Drug content^a(%)	Wetting Time^a (sec)	Water absorption ratio^a(%)	Disintegration time^b (sec)	*In-vitro* dispersion time^a (sec)
F₁	99.12 0.28	29  1.25	58.83	21  0.58	18±1.65
F₂	100.12  0.23	27  1.00	59.72	16  0.58	12±0.57
F₃	100.18  0.13	22  1.52	60.52	12  0.58	9±1.15
F₄	99.89  0.16	33  1.00	55.01	23  1.15	21±1.00
F₅	101.87  0.57	29  1.51	57.3	19  0.58	19±0.57
F₆	99.52  0.77	28  1.00	58.77	17  0.58	17±1.00
F₇	99.68  0.16	30  1.15	52.27	24  1.15	22±0.57
F₈	99.91  0.14	28  1.54	54.43	21 0.00	19±1.00
F₉	100.02  0.14	27  1.00	55.86	18  0.58	16±0.57
F₁₀	99.58 ± 0.38	38  1.15	49.23	32  0.58	24±1.00
F₁₁	99.67 ± 0.28	36  1.54	52.27	30  0.00	20±0.57
F₁₂	100.09 ± 0.36	31  1.00	54.43	24  0.58	17±1.00

a: Mean ± S.D., n = 3 tablets, b: Mean ± S.D., n = 6 tablets

Table 8. Evaluation of Formulations of Ondansetron HCl using Combination of Superdisintegrants

Formulation code	% Drug content^a	Wetting time ^a (sec)	Water absorption ratio^a(%)	Disintegration time ^b(sec)	*In-vitro* dispersion time
F₁₃	99.99 ± 0.16	26±0.321	60.93	14 ± 0.58	11±1.00
F₁₄	101.07 ± 0.42	22±0.97	64.41	10 ± 0.15	7.0 ±0.57
F₁₅	99.63 ± 0.67	23±0.73	62.52	12 ± 0.58	9.0 ±1.00
F₁₆	99.88 ± 0.16	31±0.85	54.07	18 ± 0.34	15 ±0.62
F₁₇	99.81 ± 0.31	27±0.65	58.10	15 ± 0.20	10 ± 1.00
F₁₈	100.01 ± 0.26	29±0.55	56.23	16 ± 0.19	12 ± 0.57
F₁₉	99.68±0.14	32±0.42	51.76	21 ± 0.58	17 ± 0.62
F₂₀	99.23±0.29	29±0.78	56.87	17 ± 0.43	12 ± 0.57
F₂₁	99.09±0.38	30±0.57	54.63	19 ± 0.58	10 ± 1.00

a: Mean ± S.D., n = 3 tablets, b: Mean ± S.D., n = 6 tablets

Figure 4. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F1 to F3)

Figure 5. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F4 to F6)

Figure 6. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F7 to F9)

Figure 7. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F10 to F12)

Figure 8. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F13 to F15)

Figure 9. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F16 to F18)

Figure10. Dissolution Study of Ondansetron HCl Oral Disintegrating Tablets (F19 to F21)

CONCLUSIONS:

The present study concludes that F14 formulation of oral disintegrating tablets Ondansetron hydrochloride shows release of 100.09 % drug at 8 mins. Hence from the dissolution data it was evident that F14 formulation is the optimized formulation.

ACKNOWLEDGEMENT:

We cordially acknowledge authority of Gyana Jyothi College of Pharmacy, Hyderabad, India for providing laboratory facility for our research work.

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Received on 18.09.2018 Modified on 05.10.2018

Res. J. Pharma. Dosage Forms and Tech.2019; 11(1):53-63.

DOI: 10.5958/0975-4377.2019.00009.0