INTRODUCTION:

The fast route of administration is considered as the most widely accepted route because of its convenience of self administration, compactness and easy manufacturing. But the most evident drawback of the commonly used fast dosage forms like tablets and capsules is difficulty in swallowing, leading to patients incompliance particularly in case of paediatric and geriatric patients, but it also applies to people who are ill in bed and to those active working patients who are busy or travelling, especially those who have no access to water.

For these reasons, tablets that can rapidly dissolve or disintegrate in the fast cavity have attracted a great deal of attention.

Fast dispersible tablets are not only indicated for people who have swallowing difficulties, but also are ideal for active people¹. A fast disintegrating tablet (FDT) is a solid dosage form that contains medicinal substances and disintegrates rapidly (within seconds) without water when placed on the tongue. The drug is released, dissolved, or dispersed in the saliva, and then swallowed and absorbed across the GIT². US FDA defined FDT tablets as “A solid dosage form containing medicinal substances which disintegrates rapidly usually within a matter of seconds, when placed upon the tongue.” Recently European Pharmacopoeia used the term ‘Fast dispersible tablet’ as a tablet that is to be placed in the Fast where it disperses rapidly before swallowing. Fast disintegrating tablets are also called as Fast-dissolving tablets, fast dispersible tablets, rapid melts tablets, quick dissolving tablet.

Cefdinir is a BCS class IV ^thdrug with low solubility and low permeability characteristics. Class IV^th drugs slowly dissolve in the aqueous environment of the gastro-intestinal tract after oral administration and result in a poor bioavailability, while increasing the dissolution rate will also improve bioavailability^3,4. Application of solid dispersions is one of the strategies to increase the dissolution rate of drugs^5,6. Solid dispersions consist of two (or more) component systems in which the drug is dispersed monomolecular or as small particles in a hydrophilic matrix⁷. Increased dissolution rate can be attributed to a strongly enhanced surface area of the drug for dissolution⁸. In our present study we prepared different batches of Cefdinir using polyplasdone and croscarmellose sodium and studied dissolution time of all batches.

Solid dispersion techniques have been extensively used to increase the solubility of a poorly water-soluble drug. Solid dispersion (SD) is a viable and economic method to enhance bioavailability of poorly water soluble drugs and also it overcomes the limitations of other approaches ^9,10.

MATERIALS AND METHODS:

Materials:

Cefdinir was gifted by Sura Labs, Hyderabad. PEG 4000, mannitol, polypalsdone XL, croscarmellose sodium, magnesium stearate, talc, microcrystalline cellulose were purchased from Norah traders Pvt Ltd., Hyderabad. Other chemicals were purchased from local market.

Methods:

Method of Preparation of Solid Dispersion Tablets:

Solid dispersions were prepared by solvent evaporation method. Methanol was used as solvent. Cefdinir dose was taken as 150mg.Water soluble polymers such as Mannitol, PEG 4000 and polyplasdone, croscarmellose sodium , were selected as carriers. Drug and polymers were taken in different ratios stated in the formulation chart (Table 1). The prepared solid dispersions were passed through the sieve no 20 to get uniform sized particles. The solid dispersions were mixed with required quantities of super disintegrates, diluents, lubricant and glidant. The blend was evaluated for pre-compression parameters. Then it was compressed by a single punch compression machine. The resulting tablets were subjected to evaluation various pre-compression parameters (Table 2). Then the blend was compressed by a single punch tablet punching matching ¹¹.

Table 1 Formulation of solid dispersion showing various compositions

	SD₁	SD₂	SD₃	SD₄
Drug	1000	1000	1000	1000
PEG 4000	1000	2000	--	--
Mannitol	--	--	1000	2000

Table 2 Formulation of fast dissolving tablet by using solid dispersion

	F1	F2	F3	F4	F5	F6	F7	F8	F9
Cefdinir eq.150mg	SD₁	SD₂	SD₃	SD₄	SD₁	SD₂	SD₃	SD₄	SD2
Polyplasdone XL	15	15	15	15	--	--	--	--	--
croscarmellose sodium	--	--	--	--	15	15	15	15	--
Mg.stearate	6	6	6	6	6	6	6	6	6
Talc	6	6	6	6	6	6	6	6	6
MCC	QS	QS	QS	QS	QS	QS	QS	QS	QS
Total wt	500	500	500	500	500	500	500	500	500

Evaluation of Solid Dispersion of Cefdinir:

Fourier Transform Infrared (FTIR) spectroscopy:

A Fourier Transform – Infra Red spectrophotometer was used to study the non-thermal analysis of drug-excipient (binary mixture of drug:excipient 1:1 ratio) compatibility. The spectrum of each sample was recorded over the 4000-400 cm^-1.Pure drug of Doxophylline, Drug with physical mixture (excipients) compatibility studies were performed.

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 ¹².

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 Density.

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 Density ¹³.

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 powder.

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 parameter¹⁵.

Hardness Test:

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

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 weight ¹⁶.

Drug Content:

The content of drug carried out by selected five tablets randomly in each formulation. The five tablets were grinded in mortar to get powder; this powder was dissolved in phosphate buffer pH 6.8 by sonication for 30 min and filtered through filter paper. The drug content was analyzed spectrophotometrically at 277 nm using UV sectrophotometer. Each measurement was carried out in triplicate and the average drug content was calculated¹⁷.

Disintegration test:

Six tablets were taken randomly from each batch and placed in USP disintegration apparatus baskets. Apparatus was run for 10 minutes and the basket was lift from the fluid, observe whether all of the tablets have disintegrated.

Determination of λ max:

The prepared stock solution was scanned between 200-400 nm to determine the absorption maxima. It was found to be 277 nm.

Calibration curve of Cefdinir:

The standard curve of cefdinir was obtained and good correlation was obtained with R² value 0f 0.999.the medium selected was pH 6.8 phosphate buffer ¹⁸.

Dissolution Test of Cefdinir Tablets:

Drug release from cefdinir tablets was determined by using dissolution test United States Pharmacopoeia (USP) 24 type II (paddle). The parameters used for performing the dissolution were pH 6.8 medium as the dissolution medium of quantity 900 ml. The whole study is being carried out at a temperature of 37^oC and at a speed of 50 rpm.

10 ml aliquots of dissolution media were withdrawn each time at suitable time intervals and replaced with fresh medium. After withdrawing, samples were filtered and analyzed after appropriate dilution by UV spectrophotometer¹⁹.

RESULTS AND DISCUSSIONS:

Cefdinir was mixed with various proportions of excipients showed no colour change at the end of two months, proving no drug-excipient interactions (Figure 1 and 2).

The precompression blend of cefdinir soild dispersion were characterized with respect to angle of repose, bulk density, tapped density, Carr’s index and Hausner’s ratio. Angle of repose was less than 28⁰, Carr’s index values were 9.99 to 17.1 for the precompression blend of all the batches indicating good to fair flowability and compressibility. Hausner’s ratio was less than 1.19 for all the batches indicating good flow properties (Table 3).

The results of the weight variation, hardness, thickness, friability, and drug content of the tablets are given .All the tablets of different batches complied with the official requirement of weight variation as their weight variation passes the limits. The hardness of the tablets ranged from3.0 to4.0 kg/cm² and the friability values were less than 1% indicating that the tablets were compact and hard. The thickness of the tablets ranged 4.0-5.0mm. Thus all the physical attributes of the prepared tablets were found to be practically within control limits (Table 4).

Figure 1 FTIR spctra of pure Cefdinir

Figure 2 FTIR spctra of optimized formula

Table 3 Physical properties of pre-compression blend

Formulation Code	Angle of repose (Ө)	Bulk density (gm/cm³)	Tapped density (gm/cm³)	Carr's Index (%)	Hausner's ratio
F1	25.10	0.53	0.59	10.16	1.11
F2	25.43	0.54	0.60	9.99	1.10
F3	25.41	0.52	0.58	10.3	1.11
F4	26.40	0.51	0.61	10.11	1.19
F5	27.12	0.58	0.63	10.34	1.06
F6	25.31	0.53	0.64	17.1	1.2
F7	26.11	0.56	0.63	11.11	1.12
F8	26.15	0.50	0.58	13.79	1.16
F9	28.00	0.54	0.61	11.47	1.12

Table 4 Physical evaluation of Cefdinir tablets

Formulation code	Average Weight (mg)	Thickness (cm)	Hardness (Kg/cm²)	Friability (%)	Content uniformity (%)
F1	495	4.8	3.5	0.420	95.8
F2	500	4.5	3.2	0.341	99.4
F3	496	4.9	4.0	0.363	95.3
F4	502	4.7	3.8	0.561	96.8
F5	499	4.3	3.8	0.482	97.04
F6	501	4.21	3.4	0.513	95.3
F7	497	4.0	3.2	0.412	95.3
F8	499	5.0	3.0	0.432	99.6
F9	504	4.6	4.0	0.512	98.4

Standard curve of Cefdinir was given in Figure 3.

Figure 3 standard curve of Cefdinir

The drug release rate from tablets was studied using the USP type II dissolution test apparatus. The dissolution medium was 900 ml of pH 6.8 phosphate buffer at 50 rpm at a temperature of 37 ± 0.5 °C. Samples of 5 ml were collected at different time intervals up to 1 hrs and analysed after appropriate dilution by using UV Spectrophotometer at 277nm. Dissolution data of different formulations were given in figure 4, 5 and 6.

Among all formulations F6 formulation was shown maximum drug release at 20 min i.e. 96.45%. This F6 formulation was compared with the F9 formulation which does not containing super disintegrate. F9 formulation was shown maximum drug release at 45 min. i.e. 92.38 %. Hence F6 formulation was considered as optimized formulation (Table 5 and Figure 6).

Table 5 Comparison between F6 formulation and F9 formulation

Time (min)	F6	F9
0	0	0
5	41.54	32.15
10	58.93	49.23
15	64.13	56.38
20	96.45	60.59
25		70.12
30		87.43
45		92.38
60

Figure 4 In vitro dissolution data for formulations F1 to F4

Figure 5 In vitro dissolution data for formulations F5 to F8

Figure 6 In vitro dissolution data for formulations F6 and F9

From the dissolution data it was also concluded that increase in the concentration of carrier retards the drug release.

CONCLUSION:

Among all the formulations F6 formulation containing good result that is 96.45 % in 20minutes. Hence from the dissolution data it was evident that F6 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.

REFERENCES:

1. Jaysweh J, Harani D, Rathod A, Kantilal RV. Orally disintegrating tablets, A review. Tropical Journal of Pharmaceutical Research. 2009; 8(2): 161-172.

2. Yadav VB, Yadav AV. Liquisolid granulation technique for tablet manufacturing, an overview. Journal of Pharmacy Research. 2009; 2(4): 670-674.

3. Ali AA, Gorashi AS. Absorption and dissolution of nitrofurantoin from different experimental formulations. International Journal of Pharmaceutics. 1984; 19: 297–306.

4. Remington. The Science and Practice of Pharmacy. Lippincott Wiliams and Wilkins publication. 2001.

5. Vasconcelos T, Sarmento BP. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discovery Today. 2007. 12(3): 1068–1075.

6. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. European Journal of Pharmaceutics and Biopharmaceutics. 2000; 50(4): 47–60.

7. Craig DQ. The mechanisms of drug release from solid dispersions in water soluble polymers. International Journal of Pharmaceutics. 2002; 131(8): 131–144.

8. Abu TM, Serajuddin S. Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. Journal of Pharmaceutical Sciences. 1999; 10(6): 1058–1066.

9. Amidon L, Gorden RL. Modern bioavailability, bioequivalence and biopharmaceutics classification system: new scientific approaches to international regulatory standards. European Journal of Pharmaceutics and Biopharmaceutics. 2000; 50(8):3–12.

10. Furqan A, Maulvi S, Dalwadi J, Vaishali T, Tejal G. Improvement of dissolution rate of aceclofenac by solid dispersion technique. Powder Technology. 2011; 207(10): 47–54.

11. Yang J, Kristin G, Doney J. An improved kinetics approach to describe the physical stability of amorphous solid dispersions. International Journal of Pharmaceutics. 2010; 384(11): 24–31.

12. Naji MN, Suleiman M, Malakh A. Characteristics of the in vitro release of ibuprofen from polyvinylpyrrolidone solid dispersions. International Journal of Pharmaceutics. 1986; 32(6): 229-236.

13. Praveen KP, Gnanaprakash K, GobinathM. Formulation and Evaluation of Sustained Release Tablets of Doxofylline. International Journal of Current Pharmaceutical and Clinical Research. 2014; 4(1):13-20.

14. Chethan M, Patil VR. Formulation and evaluation of sustained release matrix tablets of Metformin hydrochloride. World Journal of Pharmaceutical Sciences. 2012; 1(2): 717-730.

15. Korsmeyer RW, Gurny R, Doelker EM, Buri P. Mechanism of solute release from porous hydrophilic polymers. International Journal of Pharmaceutics.1983; 15(4): 25-35.

16. Deshpande AA, Shah NH, Rhodes CT. Sustained release drug delivery systems for prolonged gastric residence: an overview. Drug Development and Industrial Pharmacy. 1996; 22(1): 531-539.

17. Patil P, Kulkarni SV, Rao SB, Anand A, Surpur C. Formulation and In Vitro Evaluation of Mucoadhesive Tablets of Ofloxacin Using Natural Gums. International Journal of Current Pharmaceutical Research. 2011; 3(2): 93-98.

18. Wadhar KJ, Kakde RB. Formulation of Sustained Release Metformin Hydrochloride Matrix Tablets: Influence of Hydrophilic Polymers on the Release Rate and In Vitro Evaluation. International Journal of Research Controlled Release. 2001; 1(1): 9-21.

19. Jain S, Jain S, Mishra A, Garg G, Modi RK. Formulation and characterization of fast disintegrating tablets containing Cefdinir solid dispersion. International Journal of Pharmaceutical and Life Sciences. 2012; 3(12): 2190-2199.

Received on 12.06.2018 Modified on 29.06.2018

Res. J. Pharma. Dosage Forms and Tech.2018; 10(3): 169-174.

DOI: 10.5958/0975-4377.2018.00026.5