Development and Evaluation of Solid Dispersion Incorporated Topical Gel of Nabumetone

 

Suvidha Suryakant  Patil, Shriniwas Krishna Mohite

Department of Pharmaceutics, KES’s, Rajarambapu College of Pharmacy, Kasegaon. Maharashtra India

 

ABSTRACT:

The aim of present investigation was to increase dissolution rate of Nabumetone by solid dispersion technique and it is incorporated into the gel. All formulations were prepared by Kneading method and subsequently characterized and evaluated for drug release, interaction study by FT-IR, X-ray diffraction study, and DSC study from this study following points are concluded. A present study demonstrates the Kneading technique was successful for preparation of Nabumetone solid dispersion using PEG 4000, PEG 6000 and Poloxamer 188.The increased dissolution of  Nabumetone with increase in the molar ratio of polymer. Amongst all batches of solid dispersion batch F9 showed Drug content 95.24±1.03 percentage drug release 92.53±0.7 within 1 Hour. FT-IR analysis suggest the intactness of the drug in the formulations. Results of XRD and DSC confirmed amorphous formation and their stabilization. preparation of solid dispersion of Nabumetone optimized and batch was incorporated into the gel. The prepared formulations were transparent opaque in appearance with Carbopol 940.The drug content, pH, Extrudability and Spreadability was found within acceptable range.The viscosity of gel was increased as concentration of gelling agent increased.The optimum concentration of gelling agent for Carbopol 940 (0.8%w/w) was found to be good.Amongst all batches of Gel batch A2 showed Drug content 93.14±0.86  percentage drug release from diffusion study 95.68±0.59 within 1 Hour It is helpful for to improve the patient compliance toward the management of pain & inflammation topically and it overcome gastric side effect of drug.Stability study showed that the Gel formulation was stable and there is no significant change in physical properties and drug content.

 

 

INTRODUCTION:

Solid dispersions have proved to be an efficient technique for improving the dissolution rate and bioavailability of a wide range of poorly aqueous soluble drugs. The term solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. The matrix can be either crystalline or amorphous. Solid dispersion is prepared by different methods including solvent evaporation method, melting method, melt solvent method, kneading method, co-grinding method, co-precipitation method, modified solvent evaporation method, spray drying, gel entrapment technique and co-precipitation with supercritical fluid. Solid dispersion technologies are advantageous for the drugs which are poor water-soluble and highly permeable to biological membranes.  The rate limiting step for absorption with these drugs is their dissolution. Thus the rate of drug absorption can be accelerated by increasing the rate of drug dissolution.

 

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID). It is 1-naphthaleneacetic acid derivative. It is used to reduce swelling and to treat pain. It is used for osteoarthritis or rheumatoid-arthritis. It is poorly aqueous soluble drug (Water solubility 1.93g/lit at 25°C).

 

Nabumetone may cause an increased risk of serious and sometimes fatal stomach ulcers and bleeding. Elderly patients may be at greater risk. This may occur without warning signs. The present research work is planned with the aim of increasing therapeutic effectiveness of drug by increasing its skin permeation, via solid dispersion incorporated in gel. The penetration of drugs from gel across the skin mainly depends upon the aqueous solubility of drugs. Solid dispersion incorporated gel will be prepared that will improve solubility and dissolution characteristics of Nabumetone.

 

MATERIALS AND METHODS:

Nabumetone was a gift sample from IPCA Laboratories Ltd. Mumbai. Polyethylene glycol 4000, polyethylene glycol 6000, Poloxamer 188, Carbopol 940, methanol, propyl paraben was obtained from Loba Chem Pvt. Ltd (Mumbai). All the chemicals used in the present study were of analytical Grade.

 

Preparation of Nabumetone:

PEG 4000/ PEG 6000/ Poloxamer 188  Solid Dispersion:

a)  A mixture of Nabumetone and PEG 4000 / PEG 6000/ Poloxamer 188 (1:1, 1:3, and 1:5 by weight) was wetted with water-methanol (in 1:1 ratio) and kneaded thoroughly for 30 minutes in a glass mortar. The paste formed was dried under vacuum for 24 hours. Dried powder was passed through sieve no. 60 and stored in a dessicator until further evaluation. Physical mixtures (PM) were obtained by pulverizing in a glass mortar and carefully mixing accurately weighed amounts of Nabumetone and PEG4000/ PEG 6000/ Poloxamer 188.

 

Formulation and Optimization of Solid Dispersion:

Table No.1: Formulation and Optimization of Solid Dispersion

Formulation code	Drug carrier ratio	Method	Carrier
F1 F2 F3	1:1 1:3 1:5		Polyethylene glycol 4000
F4 F5 F6	1:1 1:3 1:5	Kneading method	Polyethylene glycol6000
F7 F8 F9	1:1 1:3 1:5		Poloxamer 188

 

Formulation and Optimization of Gel:

Table No.2: Formulation table of Gel.

Ingredients	A1	A2	A3
SD equivalent to 1gm of Nabumetone	4.0	4.0	4.0
Carbopol 940 (gm)	0.6	0.8	1
Methanol (ml)	5	5	5
Triethanolamine (ml)	0.2	0.2	0.2
Methyl paraben (mg)	0.002	0.002	0.002
Water (ml)	100	100	100

 

Procedure:

An accurately weighed quantity of Carbopol 940 was soaked in 100ml of water for 10 hrs. The weighed quantity of drug was dispersed in the above dispersion with a continuous stirring then required quantity of Triethanolamine was added to the soaked carbopol dispersion in order to neutralize the polymer with continuous stirring and then a definite amount of propyl paraben were added and stirring was continued for about half-an-hour to get sparky clear gel.

 

Evaluation of Solid Dispersion:

Drug Content:

Obtained SDs equivalent to 50 mg of drug prepared were weighed accurately and dissolved in a 50 ml of Methanol. The stock solutions were filtered. The solutions were then diluted suitably in same solvent. The drug content was analyzed at 261 using a UV spectrophotometer. Each sample was analyzed in triplicate.

 

Drug content (%w/w) = practically obtained mass × 100/Calculated mass

Percent yield helps to design the strategies for evaluation of product. It is mathematically calculated by using following equation.

 

% Yield= Practical yield × 100/ Theoretical yield.

 

IN-VITRO Drug Release Study:

In Vitro drug release rate of Nabumetone Phosphate Buffer solid dispersion of different samples was determined using USP dissolution test apparatus. The dissolution medium consisted of 7.4 phosphate Buffer. Samples of drug ,solid dispersion equivalent to 100mg of drug was spread onto the surface of 900ml of preheated dissolution medium at 37⁰ C. Aliquots of 5ml were withdrawn at regular intervals of time (5,10,15,20,upto 120min)and the same is replaced with fresh dissolution medium each time. The samples were measured for absorbance at 261nm.

 

FT-IR Spectroscopy:

IR Spectroscopy of optimized batch of solid dispersion was done by using FT-IR spectrophotometer (JASCO FT/IR 4100, Japan). The spectra were scanned over wavelength region of 4000 to 400 cm^-1 at resolution of 4 cm^-1. The procedure consisted of dispersing samples in KBr and comprising into pellets. The pellet was placed in the light path and the spectrum was obtained.

 

X-RAY Diffraction Studies:

X-ray diffraction pattern of drug and optimized batch of solid dispersion were traced by employing X-ray diffractometer.

 

Differential Scanning Calorimetry (DSC):

Thermogram of pure drug, were studied on a TA instrument (-). An empty aluminum pan was used as a reference. DSC measurements were performed at a heating rate of 10⁰ c/ min from 30 to 250⁰c using aluminum sealed pan.  The sample size was maintained about 3mg to 5 mg for each measurement. The sample cell was purged with nitrogen gas.

 

Physical Characterization of Gels:

Physical characterization such as Spreadability, Extrudability, viscosity, PH, drug content was measured.

 

Determination of Sprediability:

The sprediability of the formulations was determined by an apparatus suggested by Mutimer et al, which was suitable modified in the laboratory and used for the study. It consists of a wooden block which was provided by a pulley at one end. A rectangular ground glass plate was fixed on the block. An excess of gels (about 2 g) under study was placed on this ground plate. The gel was then sandwiched between this plate and another glass plate having the dimensions of the ground plate and provided with the hook. A 300gm weight was placed on the top of two plates for five minutes to expel air and provide a uniform film of the gel between the plates. Excess of gel was scrapped off from the edges. The top plate was then subjected to a pull of 30g with the help of a string attached to the hook and the time (in sec) required by the top plate to cover a distance of 10cms was noted. The sprediability was calculated using the formula.

 

S = m l/t

 

Where, s = sprediability, m = weight tied to the upper glass slide, l= length of the glass side and t = time taken in seconds.

 

Determination of Extrudability:

The apparatus used for Extrudability was suitably fabricated in the laboratory. It consist of a wooden block inclined at an angle of 45° fitted with a thin, ling metal strip (tin) at one end. While the other end was free. The aluminium tube containing 10gm of gel was positioned on inclined surface of wooden block 30gm weight was placed on free end of the aluminium strip and was just touched for 10 seconds. The quantity of gel extruded from each tube was noted.

 

Determination of Viscosity:

Viscosity of prepared gels was determined by Brook field programmable DV‐II viscometer.

 

Determination of pH:

pH of formulation determined by dispersing 0.5 gm of gel in 50 ml of water. It was checked using digital pH meter at constant temperature. Prior to this, the pH meter was calibrated using buffer solution of pH 4.0 and 9.2, and then electrode was washed with demineralised water. The electrode was then directly dipped in to gel formulation and constant reading as noted.

 

Determination of Drug Content:

One gm of solid dispersion incorporated gel was mixed with methanol, diluted to 100ml then after filtering the stock solution, filtrate was diluted suitably and absorbance was measured against blank at 261nm.

 

In Vitro Diffusion Studies for Solid Dispersion Incorporated Gels:

The in‐vitro diffusion studies for the gels were carried out by apparatus consist of cylindrical glass tube which was opened at both the ends 1gm of gel formulation equivalent to 10gm of Nabumetone was spread uniformly on the surface of cellophane membrane (previously soaked in water for overnight). Whole assembly was fixed in such a way that the lower end of tube containing gel was just touched the surface of diffusion medium i.e. 100ml PH 7.4 phosphate buffer contained in 150ml beaker which was placed in water bath and maintained at 37 ± 2°C, the contents were stirred using magnetic stirrer at 5 ± 5 rpm. The sampling was done at different time intervals over a period of 6 hours and absorbance was measured at 261 nm using shimadzu UV‐visible spectrophotometer.

 

Stability studies:

The stability of optimized formulation was monitored up to 6 month at accelerated stability conditions of temperature and relative humidity( 40⁰C ± 2⁰C RH 75 ± 5 %).Samples were withdrawn after 3 month and characterized by physical appearance, pH, Spreadability, Extrudability,        % drug content.

 

RESULT AND DISCCUSION:

Drug Content Estimation:

All the prepared gel formulations showed uniformity in drug content and were within permissible range indicating the uniform drug dispersion in the gel. The percentage drug content of various solid dispersions of Nabumetone is shown as follows.

 

Table no.:3Drug content of various batches:

Sr.No.	Batch code	Drug content
1.	F1	91.57±0.95
2.	F2	82.47±49.29
3.	F3	89.18±1.36
4.	F4	86.26±2.68
5.	F5	94.15±0.14
6.	F6	92.20±0.88
7.	F7	83.11±0.098
8.	F8	94.84±0.52
9.	F9	94.24±1.03

 

Table no: 4Diffusion study of SD incorporated gel of Nabumetone.

Sr.No	Time (min)	PEG 4000			PEG 6000			Poloxamer 188
		1:2	1:4	1:6	1:2	1:4	1:6	1:2	1:4	1:6
1.	000	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00	0.00
2.	10	2.53± 0.33	3.45± 0.34	3.53± 0.18	15.41± 0.25	11.26± 0.44	17.43± 0.42	26.62± 0.27	38.39± 0.29	40.74± 0.21
3.	20	4.51± 0.36	9.47± 0.32	10.63± 0.10	19.32± 0.19	17.53± 0.32	24.58± 0.30	35.61± 0.43	44.73± 0.14	51.28± 0.25
4.	30	10.34± 0.23	17.03± 0.18	18.41± 0.14	24.61± 0.44	26.38± 0.33	29.21± 0.54	39.46± 0.45	54.53± 0.44	59.47± 0.28
5.	40	14.05± 0.19	20.41± 0.37	32.8± 0.17	32.64± 0.56	38.34± 0.22	41.6± 0.58	43.2± 0.23	64.80± 0.39	73.61± 0.30
6.	50	17.24± 0.13	27.33± 0.22	30.63± 0.37	33.58± 0.40	45.58± 0.38	47.37± 0.32	49.72± 0.25	76.48± 0.18	83.37± 0.53
7.	60	18.46± 0.22	29.63± 0.63	38.33± 0.24	40.49± 0.34	51.77± 0.60	58.7± 0.41	57.37± 0.31	80.35± 0.27	92.53± 0.7

 

 

In-Vitro Dissolution Study:

Solid dispersions were tested for dissolution properties and compared with pure crystalline Nabumetone. Dissolution profile of drug from solid dispersions presented better dissolution performance as compared to the pure drug in a given time course. while all the solid dispersions of the drug showed 18.46±0.22 to 92.53±0.7 drug release within 1 hours. This phenomenon could be attributed to the hydrophilic character of carriers. This may be attributed to improved wettability of the drug particles, significant reduction in drug particle size during the formation of solid dispersions and intrinsically higher rate of dissolution of the selected soluble carriers, which could pull insoluble but finely mixed drug particles into the bulk of dissolution medium. The release profile observed in order F9>F8>F7>F6>F5>F4>F3>F3>F2>F1 Pure drug.

 

FT-IR Spectra of Drug and Optimized Batch:

As can be seen, a strong absorption band of C=0 stretching at 1702,C-O Stretching at 1228 ,C-H Stretching at 3053  and C-C ring stretching at 1484 cm-1. Occurs into the IR spectrum of Nabumetone. The same absorption bands at 1702 & 1605 cm-1 are present in the spectra of Solid Dispersion of Nabumetone and Poloxamer 188.The absence of any shift of carbonyl stretching band and alkenes ring stretching band suggested that know chemical interaction occurs between Nabumetone and Poloxamer 188.

 

X-Ray Diffraction:

X-ray diffraction studies were performed to reveal the crystallinity of pure Nabumetone, its dispersion with Poloxamer188. From the data, it is evident that drug exhibits crystalline nature. The XRD scan plain Nabumetone showed intense peak of crystallinity. Whereas the XRD pattern of the prepared particles exhibited reduction in both number and intensity of peaks compared to plain Nabumetone indicating the decrease in crystallinity or partial amorphization of the drug in solid dispersion system.  The XRD pattern for Drug and solid dispersion prepared with Poloxamer188 showed peak intensity with the aid of Kneading method were effective to reduce the crystallinity of pure drug.

 

FT-IR Spectrum of Nabumetone

 

Fig no:1 IR spectrum of Nabumetone \

 

Fig no:2 IR spectra of optimized batch

 

Fig no.3 XRD spectrum of Nabumetone

 

Fig no.4  XRD spectrum of Soild dispersion (optimized batch)

 

Fig no: 5 DSC of Nabumetone

 

Table no: 5 results shown in table.

Formulation	Appearance	Spreadability (g/sec)	Extrudability	pH	Viscosity(cps)
A1	Transparent	12.16	Good	6.8	10000001000000
A2	Transparent	12.67	Good	6.8	100000
A3	Transparent	11.44	Good	6.6	100000

 

Diffraction Scanning Colorimetry:

Diffraction Scanning Colorimetry of Drug:

DSC thermogram of Nabumetone and its optimized batch were presented in fig—The thermogram of Nabumetone showed sharp melting event at 79.19⁰c  with enthalpy of fusion -26.22mw.while optimized formulation were does not showed any melting endothermic event reveals drug in amorphous state.

 

DSC Of Solid Dispersion optimized batch

 

Fig.no:6 DSC of solid dispersion

 

The Formulated Gels Were Evaluated For Various Parameters:

Topical application of the drug at the effected site offers potential advantages of delivering the drug directly to the site of action. Skin injuries or local infections can best be treated by application of products which form transparent water vapour and air permeable film over the skin surfaces from which the drug releases continuously to the desired site. The present work deals with formulation and evaluation of Nabumetone topical gel using gelling agent carbopol 940 in different concentrations and all the raw materials are of standard grades as supplied by the manufacturer.  The formulated Nabumetone carbopol 940 gels were white transparent and opaque in appearance. The pH of all gel formulation was found between 6.8, 6.8 and 6.6 which lies in normal pH range of the skin. Viscosity is important parameters for characterizing the gels as it effect the Spreadability, Extrudability and release of the drug, all formulated Nabumetone gels showed in increased viscosity as the concentration of the gelling agent was increased. The extrusion of gel from the tube is an important during application and for the patient compliances. Gel with high consistency may not extrude from the tube easily, whereas low viscous gels may flow quickly, Extrudability of gel.

 

Drug Content:

All the prepared gel formulations showed uniformity in drug content and were within permissible range indicating the uniform drug dispersion in the gels.

 

Table no: 6 Drug content of SD incorporated gel of Nabumetone

Sr. No.	Batch code	Drug Content
1.	A1	94.23±0.64
2.	A2	96.65±0.32
3.	A3	93.14±0.86

 

Diffusion Study:

In-vitro release studies were carried out by using phosphate buffer pH 7.4.Release of Nabumetone from all prepared gel formulations was found to be increased.

 

Table no: 7 Diffusion study of SD incorporated gel of Nabumetone.

Sr.No.	Time (min)	A1	A2	A3
1.	10	16.02±2.03	39.16±0.41	26.57±0.24
2.	20	36.89±0.75	54.61±0.21	30.50±0.36
3.	30	57.24±0.37	68.4±0.51	47.37±0.32
4.	40	68.65±0.06	75.89±0.42	62.69±0.26
5.	50	74.37±0.49	89.42±0.37	78.23±0.24
6.	60	86.8±0.97	95.68±0.59	82.91±1.01

 

Stability Study:

The stability study of optimized Gel formulation (A2) was carried out at accelerated condition of temperature 40⁰C ± 2°C RH 75 ± 5 %

 

Table No 8 stability study of optimized Gel formulation

S. No.	Parameters	At temperature 400C ± 20C RH 75 ± 5 %
		Zero month	Three month	Six month
1.	Physical appearance	Transparent	Transparent	Transparent
2.	Spreadability	12.65	12.49	12.23
3.	Extrudability	Good	Good	Good
4.	pH	6.8	6.8	6.7
5.	Drug Content	96.65±0.32	95.93±0.18	94.03±0.42

 

CONCLUSION:

The in vitro diffusion study of Nabumetone solid dispersion incorporated gels was greatly improved when compared with those of intact Nabumetone incorporated gels. From overall formulations F9 was found to be the best formulations. From the above results, it may be concluded that solid dispersion incorporated Gels were better for improvement of dissolution and diffusion of Nabumetone and also to overcome gastric side effect of the drug.

 

REFERENCES:

1.        Zatz J.L., Kushla G.P., Lieberman H.A., Rieger M.M., Banker G.S. Gels In: Pharmaceutical dosage form: Disperse system. New York: Marcel Dekker.2nd ed; 399-421; 2005.

2.        Ahuja S, Scypinski S. Handbook of modern pharmaceutical analysis. Academic press. 247;2005.

3.        Chowdary K. P. R.,K. Ravi Shankar M., Subbalakshmi. Recent Research on Solid Dispersions - A Review. Journal of Global Trends in Pharmaceutical Sciences. 5(2); 1612-1623; 2014.

4.        Bakhle S.S., Upadhye K.P., Dixit G.R., Wadetwar R.N. Solubility and Dissolution Improvement of Poorly Soluble Drug Using Solid Dispesion Technique. International Journal of Pharmacy & Technology. 2(4); 1230-1240; 2010.

5.        Costa P ,Lobo JMS. Modelling and comparison of dissolution profiles. Eur J Pharm Sci. 13;123-33; 2001.

6.        Brahmankar D.M ,Sunil B,Jaiswal, Bioavailability and Bioequivalence, Biopharmaceutics and pharmacokinetics A treatise,II edtn, Vallabh prakashan,2009,349-357.

7.         Chiou W.L., Riegelman S. Pharmaceutical application of solid dispersion. J Pharm Sci.60;1281-1302; 1971.

8.        Misra Sruti Ranjan, Ellaiah P, Jena Prabhat Kumar , Nayak Bhabhani Shankar, Mishra Gitanjali .Comparative Study on Effect of Solid Dispersion Techniques For Enhancement of Solid Dissolution Rate of Pioglitazone HCl. International Research Journal of Pharmacy 2(8);136-141;2011.

9.        Tejas Patel, Timir Patel, Sunil Makwana, Tushar Patel. Enhancement of dissolution of Fenofibrate by Solid dispersion Technique. International Journal of Research in Pharmaceutical Sciences. 1(2);127-132;2010.

10.     Vidyadhara S, Babu P.S., Swapnasundari P, Rani M.T., Solid Dispersion: An approach to improve sold formulation development. Pharma Bioworld. 2; 70-76; 2004.

11.     Ganesh Chaulang, Kundan Patil, Dhananjay Ghodke, Shagufta Khan, Pramod Yeole. Preparation and Characterization of Solid Dispersion Tablet of Furosemide with Crospovidone. Research Journal of Pharmaceutical and Technology.1 (4); 386-389; 2008.

12.     Thakur V, Prashar B, Arora S , Formulation and in vitro Evaluation of Gel for Topical Delivery of Antifungal Agent Fluconazole Using Different Penetration Enhancers, Drug Invention Today,2012; 4(8): 414-19.

13.     Mutimer M.N. Riffikin C, Hill J.A., Marry E, Cry N.G, Gliekman G.J.Am Pharm, Assoc. Sci. 45; 212; 1956.

14.     Liberman H.A, Rieger M.M, Banker G.S. Pharmaceutical Dosage Forms: Disperse systems.Marcel Dekker. NY. 549; 1989.

15.     Gupta G.D., Gaud R.S. Release rate of tenoxicam fram acrypol gels. The Indian Pharmacist. 69 -75; 2005.

16.     Shanmugan S, Cendil Kumar A, Vetrichelvan J, Manavalan R, Venkappayya D .Spectro photometric method for theestimation of aceclofenac in tablets. Indian Drugs Feb. 42(2);106 - 107; 2005

17.     Sanjay, Jain B.D., Amol P, Patel K, Vinod M. Formulation development and evaluation of fluconazole gel in various polymer bases. Asian Journal of Pharmaceutics.1(1);63- 68 ;2007.

18.     Loveleen Preet Kaur, Tarun Kumar Guleri. Topical Gel: A Recent Approach for Novel Drug delivery Asian Journal of Biomedical and Pharmaceutical Sciences. 3(17) ;1-5;2013.

19.     Wadke D.A., Serajuddin A, Jacobson H, “Preformulation testing”. In: Lieberman H.A.,   Lachman L, Schwartz J.B., eds. Pharmaceutical Dosage Forms: Tablets. New York, NY: Marcel Dekker; 1989:1-73.

20.     Aml Mekkawy, M. Fathy and Sohair E. Shanawany. Formulation  and In vitro Evaluation of Fluconazole Topical Gels. British Journal of Pharmaceutical Research.3(3);293-313;2013

21.     Saleem M.A., Sumanji Bala. Formulation & Evaluation of Meloxicam Solid Dispersion Incorporated Topical Gels. International Journal of Pharma and Bio Sciences. 1(3); 1-9; 2010.

22.     Dr. C.S. Chauhan, Dharmendra singh sisodiya, Formulation and Evaluation of Fluconazole solid dispersion incorporated gel using polymers as controlled release dosage forms: Development, characterization and in vitro evaluation. International Bulletin of Drug Research.3 (4);1-10;2013.

23.     Prasobh GR, Mohammed Sabir AS, Sameera FA, Nooruddeen  K,  Jyothi B Nair. Solid Dispersion of Nabumetone In Ethyl Cellulose an Approach to Enhance the Solubility and Dissolution Rate. Hygeia.1(1);33-35;2009.

24.     Thakur N, Pratibha B, Mahant S, Rao R, Formulation and Characterization of Benzoyl Peroxide Gellified Emulsions, Scientia Pharmaceutica, 2012; 80:1045–60.

25.     Gallagher S, Trottet L, Heard C, Ketofrofen release from permeation across and rheology of simple gel formulation that stimulate increasing dryness, International journal of pharmaceutics,2003;268:37-45.

26.     D.Akiladevi , P.Shanmugapandiyan, D. Jebasingh , Sachinandhan Basak. Preparation and Evaluation of Paracetamol By Solid Dispersion Technique. International Journal of Pharmacy and Pharmaceutical Sciences. 3(1); 188-189; 2011.

27.     R. Kumari, P. Chandel, A. Kapoor. Paramount Role of Solid Dispersion in Enhancement of Solubility. Indoglobal Journal Of Pharmaceutical Science.3(1); 78-89;2013.

28.     Aftab Modi, Pralhad Tayade. Enhancement of Dissolution Profile by Solid Dispersion (Kneading) Technique. AAPS Pharm Sci Tech. 7(3); E1-6; 2006.

29.     Nagarajan K., Gopal Rao M. , Satyajit Dutta, Pavithra R., Swetha G. Formulation and Dissolution Studies of Solid Dispersions of Nifedipine.Indian Journal of Novel Drug Delivery.2 (3); 96-98; 2010.

30.     Prasadarao C.V., Nagabhushanam M.V. Enhancement of Dissolution Profile of Mefenamic Acid by Solid Dispersion Technique. International Journal of Research In Pharmacy and Chemistry. 1(4); 1127-1134; 2011

31.     Prasanthi N.  , Rama Rao N., Manikiran S. Studies on Dissolution Enhancement of Poorly Water Soluble Drug Using Water Soluble Carriers.Asian Journal of Pharmaceutical and Clinical Research.3(2); 95-97; 2010.

32.     Farzana S. Bandarkar, Ibrahim S. Khattab. Lyophilized Gliclazidepoloxamer Solid Dispersions For Enhancement Of Invitro Dissolution And Invivo Bioavailability. International Journal Of Pharmacy And Pharmaceutical Sciences.3 (2); 122-127; 2011.

33.     Goldberg A.H., Gibaldi M, Kanig J.L. Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures. II. Experimental evaluation of eutectic mixture: urea-acetaminophen system. J Pharm Sci.55;482-487;1966.

34.     Ducan C.Q.M, Paul R.G., Kett V.L., Hopton M.L. The relevance of the amorphous state to pharmaceutical dosage forms: Glassy drugs and frezze dried systems. Int. J. Pharm. 179;179-207;1999.

35.     Manish K.G., Yin-Chao T. David Goldman, Robin H. Bogner Hydrogen bonding with adsorbent during storage governs drug dissolution from solid dispersion granules. Pharm Res.19;1663-1672;2002.

36.     Deshpande O.A., Yadav V. B. Improvement in Physicochemical Properties of Indomethacin by Melt Granulation Technique. International Journal of ChemTech Research. 1(4);1312-1317;2009.

37.     Ahire B. R., Rane B. R., Bakliwal S. R., Pawar S. P. Solubility Enhancement of Poorly Water Soluble Drug by Solid Dispersion Techniques International Journal of PharmTech Research. 2(3); 2007-2015;2010.

 

 

 

Received on 24.08.2014          Modified on 10.09.2014

Accepted on 07.10.2014         © RJPT All right reserved