1. INTRODUCTION:

The solubility of drug is one of the most important standards in formulation development. oral bioavailability of drugs depends upon its solubility as well as dissolution rate, these drugs having identical low solubility in biological fluids, which results into poor bioavailability after oral administration. solid dispersion is one of the tactics to improve solubility and hence bioavailability of poorly water soluble drugs. Solid dispersion processes are have taken sizable interest of improving the dissolution rate of highly lipophilic drugs thereby maximizing their solubility by reducing drug particle size, improving wettability and forming the amorphous particles.¹ The term solid dispersion defined to a set of solid products consisting of at least two different components, generally a hydrophilic inert carrier and a hydrophobic drug. naproxen sodium is nsaid drug under the bcs class ii. drugs giving the low aqueous solubility and high membrane permeability are classified as class ii drugs. therefore, solid dispersion technology are particularly auspicious for bettering the oral absorption and bioavailability of bcs class ii drugs. in case of solid dispersion, drug is dispersed in the matrix normally a hydrophilic matrix and a hydrophobic drug, thereby developing a solid dispersion.²

a) Solubility:

• In the other word the solubility can also define as the ability of one substance to form a solution with another substance.

• The substance to dissolved is called as solute and dissolving fluid in which the solute dissolve is called as solvent which together form a solution the process of dissolving solute into solvent is solution or hydration if the solvent in water³.

• Almost more then 90% drug are orally administered drug adsorption, sufficient and reproducible bioavailability, pharmacokinetic profile of orally administered drug substance is highly dependent on solubility of that compound of tha solubility in aqueous medium, more the 90% drug can approved since 1995 have poor solubility. it is compute then 40% of active new chemical intermediaries pointed out in combinational screening program employed by many pharmaceutical companies are poorly water soluble⁴.

• Solubility is one of the important parameter to achieve desired concentration of drug in systemic circulation for achieving required pharmacology response.^5,6

2. MATERIALS AND METHODS:

Material:

Chemicals:

Naproxen Sodium Pure Drug was purchased from Balaji Drugs, Nashik, Maharashtra, India. Polyethylene Glycol grade 4000 was purchased from fine Chemicals, Mumbai, India. Polyvinylpyrrolidone K30 was purchased from fine chemicals, Mumbai, India. All the other reagents obtained from research lab.

Instrumentation:

The work was accomplished on a UV- visible spectrophotometer (modelcUV-3000⁺ Labinndia). Tablet compression machine was manufacture by Cemach Machinaries Ltd. Ahmedabad (model no. 8 station, D). The FTIR spectra of API and its excipients were secure by Fourier Transform Infrared Spectrophotometer (Aglient Technologies). All weighing was done on electronic precision balance (Wenser PGB220).

Methods:

Preparation of solid dispersion:

Solvent evaporation technique:

In this method, drug and polymer dissolve in common organic solvent and the solvent is evaporated at low temperature. At that point, the subsequent blend is milled through reasonable screens⁷. A portion of the items are not appropriate in this technique on the grounds that solitary single solvent is used in this cycle. In the event that drug is solvent in one solvent and polymer is broken down in one more solvent at the hour of evaporation, solvents are evaporated dependent on boiling point, so drug or polymer solidified immediately dependent on the solvent utilized⁸. It will prompt not complete polymorphic change happens. So, at long last makes a low soluble and low dissolution rate. Subsequently, drug and polymer disintegrate in single solvent as it were⁹. The selection of polymer depends on drug nature and soluble of drug in organic solvent. All in all, solvents utilized ethanol, acetone, isopropyl alcohol, and dichloromethane^10,11.

Table no.1. Formula for Naproxen sodium solid dispersion

Batch code	Method	Ratio	Drug	Excipients
SD1	Solvent evaporation method	1:1	Naproxen sodium	PEG 4000
SD2		1:2	Naproxen sodium	PEG 4000
SD3		1:3	Naproxen sodium	PEG 4000
SD4		1:1	Naproxen sodium	PVP-K30
SD5		1:2	Naproxen sodium	PVP-K30
SD6		1:3	Naproxen sodium	PVP-K30

3. RESULT AND DISCUSSION:

Characterization of physicochemical properties of drug:

Organoleptic properties:

Color - White

Nature - crystalline powder

Odor - Odorless

Pre-formulation study:

Physical constant:

Melting point of naproxen sodium was examine by capillary fusion method. It was found to be 260^oC to 262^oC.

Solubility profile of drug:

solubility of naproxen sodium was determined by flask shaking method. It was found to be,

Insoluble in water, slightly soluble in ether, sparingly soluble in ethanol and freely soluble in methanol.

Stability study of Naproxen sodium with excipients:

Table no.2. compatibility study of drug with excipient

Sr. no.	Naproxen sodium + Excipients	Observations
Sr. no.	Naproxen sodium + Excipients	Intial (color)	After 15 days
1	PVP-K30	White powder	No change
2	PEG 4000	White powder	No change

Preparation procedure for calibration curve of naproxen sodium:

The absorbance of the solution was measured at 272 nm using UV-visible spectrophotometer.

A graph of the concentration vs absorbance was plotted. Table no.5.

Characterization of uv-visible spectrophotometer:

a) Detection of max:

Spectrum of drug - Methanol

max – 272 nm

Fig.1. UV-Visible spectrum

Table no.3. Concentration/ Abs. table

Concentration (µg/ml)	Absorbance (nm)
10	0.113
20	0.145
30	0.225
40	0.295
50	0.375
60	0.434
70	0.532
80	0.581
90	0.676
100	0.755

Fig.2. calibration curve of naproxen sodium in methanol

Drug - Excipient study by FTIR:

The physical mixture of Naproxen sodium, PVP-K30 and PEG 4000 were kept under compatibility study for temperature 40˚C ± 75 RH for period of two weeks. They were found to be without any singnificant physical changes. Therefore it is confirmed that all the active and inactive excipients which were kept under compatibity study are compatible with each other all these ingradients were selected and used in present work^12,13.

Table no.4. Interpretation of FTIR peak present in naproxen sodium

S. No.	Wave number in formulation (cm^-1)	Characteristic Wave number range (cm^-1)	Bond nature and bond attributed
1	3091	3000-3700	O-H Stretching
2	1684	1600-1700	C-C Stretching
3	818	600-900	C-H Rocking
5	2942	2700-3300	C-H Stretching
6	1604	1600-1900	C=O Stretching
7	1394	1200-1500	O-H Bending

Fig.3. FTIR Spectra of naproxen sodium

Fig.4. FTIR Spectra of naproxen sodium : PVP-K3

Solubility study:

Naproxen sodium solid dispersions were prepared by solvent evaporation method with their respective carriers. After preparation of solid dispersion solubility analysis was carried out. The formulation (SD6) in the ratio of 1:3 shown highest solubility i.e. 4.218 ± 0.17 mg/ml, almost 68-fold compared to that of the pure drug (Pure drug solubility is 0.068 ± 0.13 mg/ml. The results are given as graphical representation in Fig.7.

Fig. 5. solubility studies of naproxen sodium solid dispersion

Percentage practical yield:

Percentage practical yield was calculated to know about percent yield or efficiency of any method and help in selection of appropriate method of production¹⁷.

Drug content:

Solid dispersions equivalent to 20 mg of Naproxen sodium was weighed accurately and dissolved in 100 ml of methanol. The solution was filtered, diluted suitable and drug content was analysed at λmax 272 nm against blank by UV spectrometer.

Fig.6. % practical yield / drug content

Pre-compression evaluation tests:

Pre-formulation studies: Prior to compression, solid dispersions were evaluated for their characteristic pre-compression parameters, such as bulk density, tapped density, Hausner ratio, Car’s compressibility index and angle of repose^14,15,16.

Post compression evaluation tests:

Post compression parameters like Weight Variation, Thicknesses, Hardness, Friability, Content Uniformity and in vitro disintegration time studies were performed^17,18.

Table no.5. Pre-compression Evaluation of formulation (Tablet)

Formulation code	Bulk density	Tapped density	Angle of repose	Carr’s index	Hausner’s ratio
SD1	0.47±0.12	0.57±0.06	27.40±0.76	15.04±0.98	1.18±0.01
SD2	0.48±0.15	0.55±0.08	25.06±0.98	12.32±0.87	1.19±0.02
SD3	0.46±0.18	0.53±0.087	24.38±0.76	13.20±0.76	1.13±0.01
SD4	0.43±0.9	0.49±0.065	23.62±0.86	12.44±0.56	1.14±0.01
SD5	0.41±0.98	0.47±0.043	21.97±0.76	14.66±98	1.16±0.02
SD6	0.46±1.1	0.58±0.076	23.08±0.54	12.21±69	1.17±0.01

Table no.6. Post compression Evaluation of formulation (Tablet)

Sr. no.	Formulation code	Weight variation (mg)	Diameter (mm)	Thickness (mm)	Hardness (Kg/cm²)	Friability (%)	Disintegration (min.)
1	SD1	499±0.5	11±0.1	5.1±0.06	3.44±0.98	0.60±0.7	21±1.7
2	SD2	505±1.2	11±0.06	5.2±0.07	3.50±0.65	o.51±0.05	25±0.77
3	SD3	500±1.4	11±0.04	5.1±0.08	3.84±0.56	0.49±0.15	31±0.89
4	SD4	496±0.6	11±0.04	5.2±0.09	3.52±0.48	0.50±0.06	23±1.5
5	SD5	498±0.8	11±0.03	5.0±0.05	3.75±0.76	0.65±0.14	27±1.2
6	SD6	500±0.5	11±0.02	5.1±0.09	3.74±0.87	0.68±0.13	24±0.98

Table no.7. In-vitro drug release of naproxen sodium 0.1N HCl

Time	Naproxen sodium	SD1	SD2	SD3	SD4	SD5	SD6
0	0	0	0	0	0	0	0
15min	37.58	39.68	40.89	46.12	45.34	46.05	47.21
30min	38.64	41.39	41.39	47.23	46.92	47.5	49.92
45min	40.35	42.47	42.84	48.23	48.21	48.34	50.92
60min	41.98	44.34	43.34	49.13	50	50.36	51.07
75min	42.73	45.26	44.26	51.14	51.07	51.71	52.23

In-vitro Disintegration study:

The USP gadget to rest disintegration was six glass tubes that are "3 long, open at the top, and held against 10" screen at the bottom finish of the basket rack gathering. One tablet is set in each cylinder and the basket rack is harmed in 1liter beaker of water at 37 ± 2ºC, to such an extent that the tablets stay underneath the outside of the liquid on their vertical development and plummet not nearer than 2.5 cm from the bottom of the beaker¹⁹.

In-vitro Dissolution study:

Dissolution studies of solubility enhanced dispersions were performed in a calibrated 8 station dissolution test apparatus equipped with paddles (USP apparatus II method) employing 1000 ml of purified water as a medium¹⁶. The paddles were operated at 50 rpm and temperature was maintained at 37 ºC ± 1ºC throughout the experiment²⁰.

Fig.7. In-vitro dissolution profile

CONCLUSION:

The study of solubility enhancement of naproxen sodium using different carriers by solid dispersion technique revels following conclusion,

· The solid dispersion prepared by solvent evaporation method were found to be white in color, fine and free flowing powders with uniform drug content.

· FTIR spectroscopic studies indicated that there was no drug-excipients interaction.

· In their 6 formulation (SD1-SD6) the Percentage practical yield for all formulations of solid dispersions were prepared among SD6 found to be promising 98.97%.

· Solubility of naproxen sodium was increased as the concentration of carriers increased.

· The comparison between pure drug and formulations is done through solubility study and In-vitro study. The formulations are shown as better solubility and bioavailability, in that PVP-K30 Containing formulations better solubility than PEG 4000 formulation.

ACKNOWLEDGEMENT:

We are grateful to the teacher’s and Principal of Loknete Dr. J. D. Pawar College of Pharmacy, Manur, Tal. Kalwan for their helpful guidance.

REFERENCES:

1. Mayersohn M., Gibaldi M. et al New method of solid state dispersion for increasing dissolution rates. J Pharm Sci. 1966; 55: 1323-1342.

2. Taylor L.S., Zografi G. et al Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res. 1997 14(12): 1691-1698.

3. Chirag A. Patel, Priyal R. Patel, Dhrubo Jyoti Sen, Jayvadan K. Patel. et al Enhancement of Solubility of Poorly Water-Soluble Drug (Allopurinol) Through Solid Dispersion. Research J. Pharma. Dosage Forms and Tech. 2010; 2(2):156-163.

4. Constantinides P.P. et al Lipid micro-emulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects, Pharm. Res. 1995; 12; 1561 1572.

5. Jung J., Perrut M. et al Particle design using supercritical fluids: literature and patent survey, J. Supercrit. Fluids 2001; 20; 179 219.

6. Kakumanu V. K., Bansal A. K. et al Supercritical Fluid Technology in Pharmaceutical Research. Businessbriefing: Labtech, 2004; 70-72.

7. Kaushal, A.M, Guptam P., and Bansal, AK. et al Amorphous drug delivery systems: molecular aspects, design, and performance. Crit. Rev. There. Drug Carrier Syst., 2004; 21(3): 133-193.

8. Leuner C., Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000; 50(1): 47-60.

9. Majerik V., Horvath G., Charbit G., Badens E., Szokonya L., Bosc N., Teillaud E. et al Novel particle engineering techniques in drug delivery: review of formulations using supercritical fluids and liquefied gases, Hun. J. Ind. Chem. 2004; 32; 41 56

10. Mayersohn M., Gibaldi M. New method of solid state dispersion for increasing dissolution rates. J Pharm Sci. 1966; 55: 1323-1342.

11. Dong Z, Chatterji A, Sandhu H, Choi DS, Chokshi H, Shah N. et al Evaluation of solid state properties of solid dispersions prepared by hot-melt extrusion and solvent co-precipitation. Int J Pharm. 2008; 355(1-2): 141-149. doi:10.1016/j.ijpharm.2007.12.017.

12. Murali Mohan Babu GV, Prasad ChD, Ramana Murthy KV. et al Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine. Int J Pharm. 2002; 234(1-2): 1-17. doi:10.1016/S0378-5173(01)00925-5.

13. Spencer CM, Wilde MI. et al Diacerein. Drugs. 1997; 53(1): 98-106.

14. Fidelix T, Macedo CR, Maxwell LJ. et al Diacerein for osteoarthritis. Cochrane Database. 2006.

15. Dougados M, Nguyen M, Berdah L, Mazieres B, Vignon E, Lequesne M. et al Evaluation of the structure modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the Chondromodulating Effect of Diacerein in OA of hip. Arthritis Rheum. 2001; 44(11): 2539-2547.

16. Smith GN, Myers SL, Brandt KD, Mickler EA, Albrecht ME. et al Diacerhein treatment reduces the severity of osteoarthritis in the canine cruciate deficiency model of osteoarthritis. Arthritis Rheum. 1999; 42(3): 545-554. doi: 10.1002/1529-0131(199904)42:3<545:AID-ANR20>3.0.CO;2-4.

17. Felisaz N, Boumediene K, Ghayor C, Herrouin JF, Galerra P. et al Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1. Osteoarthritis Cartilage. 1999; 7(3): 255-264. doi: 10.1053/joca.1998.0199.

18. Mogal Prasad S, Dode Raj H, Surawase Rajendra K. et al Solid dispersion: A magnificent app. to improve sol. of poorly soluble drugs. Ejbps,2021;8(5): 171-176.

19. Gao D, Wu JS, Lu WS, Chen S, Kuo PC, Chen CM. et al. Pharmaceutical composition containing diacerein. US 2010/0104651A1. TWi Biotechnology Inc. 2010; 4: 29.

20. Zografil G, Newman A. et al Introduction to amorphous solid dispersions. In: Gad SC (ed). Pharmaceutical Amorphous Solid Dispersions. 1st edition, John Wiley & Sons, Inc. 2015. doi: 10.1002/9780470571224.pse522.

Received on 22.05.2021 Modified on 29.08.2021

Asian J. Pharm. Tech. 2022; 12(1):1-5.

DOI: 10.52711/2231-5713.2022.00001