A Novel approach to develop Etodolac Emulgel with Alkaloidal Penetration Enhancer

 

Adity Singh1*, Saurav S Ghosal1, KM. Diksha S Singh2, Dr. Manoj Mishra2,

Jayant Kumar Maurya3

1Department of Pharmaceutics, Shambhunath Institute of Pharmacy, Jhalwa, Prayagraj,

Uttar Pradesh - 211012, India.

2Department of Pharmacology, Shambhunath Institute of Pharmacy, Jhalwa, Prayagraj,

Uttar Pradesh - 211012, India.

3Ashok Singh Pharmacy College, Jaunpur, Uttar Pradesh, India.

*Corresponding Author E-mail: sadity104@gmail.com

 

ABSTRACT:

The aim of present study is to development of novel formulation present unique challenge. The topical route has long been used for delivering drugs directly to the affected target site through the skin. Current approaches in design and optimization of topical formulation necessitate extensive decisions in choosing the right components for the formulation to achieve high safety clinical efficacy and patient compliance it was concluded that etodolac emulgel formula could be very promising topical alternative for the conventional dosages from provide sustained and prolonged delivery of drugs. The results of this research establish a new and useful approach in designing the oil phase of a formulation where the active ingredient needs to be dissolved in the oil phase and develop emulgel system. Additionally, the use of emulgels for topical delivery of hydrophobic drugs has been found to be better at achieving a higher drug concentration over a longer period of time across the skin barrier as compared to gels.

 

KEYWORDS: Emugel, Hydrophobic drugs, Sustained, Etodolac.

 

 


INTRODUCTION:

The goal of each drug delivery system (DDS) is to supply the correct site in the body with a therapeutic quantity of medication in order to achieve the desired drug concentration on time and then retain it (Alfonso RG et al., 1985 and Chein YW, 1981). A valuable brunt on the clinical effect of a medication is the path of administration (Robinson RJ et al. 1987). Some of these DDS are made of polymer which is which.

 

Topical Drug Delivery:

Topical drug delivery systems allow targeted administration of active molecules/therapeutic agents via skin, vaginal, ophthalmic and rectal routes anywhere in the body (Walters KA, 2002). Topical formulations include a wide range of formulations designed to suit both cosmetic or dermatological applications and diseased skin. Those formulations are physicochemical in nature. These formulations range from solid to semisolid to liquid in physicochemical nature (Prajapati MK et al., 2013).

 

Skin: the target organ:

Skin is an important barrier to topical drug trafficking and its critical purpose is to prevent harmful/inactive compounds through it. Thus, skin plays a key role in protecting the body from a number of biological and chemical environmental affronts (Bucks Daniel et al., 2002). As seen in Figure 1, the furthest epidermis, which is avascular and vascular dermis, is formed in the skin. Dermis also contains the free nerve endings which are responsible for sensation of pain.

 

Fig.1: Diagram showing various layers of skin

 

Emulgels:

If a mixture of gel and emulsion is used, the drug type is referred to as emulgel. Gels are currently gaining consideration for the topical use of drugs, particularly hydrogel formulations, while they have a beautiful look and expand nice cool sensation. Gel formulations' pharmacological activity cannot change as easily as the solution process (Jain A et al., 2010 and Yassin Gc, 2014); Emulgels are developed and used to overcome this constraint, so that even a hydrophobic therapeutic moiety can have the special properties of gels (Patel J et al., 2014).

 

Eumlgels is the mixture of emulsion and gel that are hydrogels containing randomly distributed microdroplets of oil [Fig. 3] (A et al. Jain, 2010). They are also emulsions of the form o/w or w/o, gelled by mixing with gelling agent. They have recently been used as vehicles for transporting various drugs into the skin (Singla Vet al., 2012) and the vagina (Nair R et al., 2010).

 

Fig. 2: General structure of Emulgel system

 

MATERIALS AND METHOD:

The supplier used the following products, which were either AR/LR grade or the best available pharma grade, as supplied. The list of materials used in the current studies along with the manufacturers was provided in Table 1.

Table 1: Materials and Their Suppliers

S. No

Name of material

Brand Name

1.

Piperine

Lab extract

2.

Capsaicin

Lab extract

3.

Carbopol 940

S.D. Fine Chemicals

4.

Tween 20

S.D. Fine Chemicals

5.

Span 20

S.D. Fine Chemicals

6.

Light liquid paraffin

S.D. Fine Chemicals

7.

Sodium hydro oxide

Qualigenic fine chemical

8.

Purified water

Inhouse

9.

Propylene glycol

Qualigenic fine chemical

14.

Etodolac

IPCA Laboratories

15.

Triethanolamine

Qualigenic fine chemical

16.

Methyl cellulose

Qualigenic fine chemicals

18.

Methyl Paraben

S.D. Fine Chemicals

19.

Parabens

Cyper pharma

             

METHODOLOGY:

Preformulation studies:

Studies of preformulation apply to exploratory practices starting in the initial stages of production of the formulation. Studies on preformulation are designed to classify the bulk material, assess the compatibility of initial excipients with the active ingredient, and improve analytical methods to be used during the production of formulations.

Therefore the program 's goals are (Gopinath et al. 2011; Tushar et al. 2012):

·       To determine the physicochemical parameters required for a new drug substance.

·       Determining the profile of its kinetic volume.

·       Determining its physical properties.

·       To establish its compatibility with excipients.

 

Preformulation experiments on the drug sample collected therefore include color, measurements, analyzes of the solubility, assessment of the melting point and experiments of compatibility.

 

Solubility:

The drug's solubility was calculated by taking some quantity of drug (about 1-2mg) separately in the test tube and adding 5ml of solvent (water, ethanol, methanol, 0.1N HCl, 0.1N NaOH, chloroform, and 7.4 pH buffer) Shake vigorously and held for some time. Notice the solubility of the product (at room temperature) in different solvents.

 

Melting point determination:

Melting point was recorded on digital capillary melting point apparatus.

 

Partition coefficient:

This is a calculation of the lipophilicity of a product and an example of its capacity to move cell membrane along with octanol/water and chloroform/water, is the oil/ water partition coefficient in method. The partition coefficient is defined as the ratio of unionized drug disbursed in equilibrium between the organic and aqueous phases. It provides a way of characterizing the drug's lipophilic/hydrophilic nature.

 

Procedure:

Taken properly wiped separating funnel clean and dry, then transferred the octanol/water method (50:50 20ml) as sufficient quantity in separating funnel and added the 10mg drug into it. Funnel was constantly shook until the medication was dispensed equally in both processes. Then it is put on stand for each of the phases to be settled. UV spectroscopy (IP, 2010 and SB Shirsand et al., 2012) is calculated after that both phases were separated in beaker and the amount of drug in each process.

 

Drug excipients compatibility studies:

Application of (ETO) powder mixed with potassium bromide and pressed in the shape of a disc and combination of the drug with excipients/polymer was performed to examine any changes in the drug's chemical composition after it was combined with the excipients/polymers. Shimadzu FTIR spectroscopy (4000-400) cm-1 analyzed the disk.

 

Standard calibration curve for etodolac:

100mg of ETO was correctly measured and dissolved in a small volume of methanol, and made up of methanol up to 100ml. 10ml was pipetted out of this primary solution and brought up to 100ml with a saline pH 7.4 buffered with phosphate. Aliquots were taken from this secondary solution to obtain concentration of 2-10μg/ ml. In the UV- Visible Spectrophotometer (Shimadzu) the absorbance of the resulting solution was calculated at 274nm using phosphate buffered saline pH 7.4 with little methanol as blank. The standard curve was plotted for X- axis concentration and Y- axis absorption (SB Shirsand et al., 2012, Carstensen, 1996; Wadke et al. 1980).

 

Formulation:

Extraction of piperine:

Take 150ml of 95% ethanol in round bottom flask, and add 5-10 boiling chips. In the soxhlet apparatus take 15 gm of black pepper powder and heat the reflux for 2-2,5 hours. Subsequently the collected round bottom flask mixture was filtered using suction pump. So by simply distilling concentrate the filtered solution to a volume of 15-20ml. Took the concentrated pepper extract in Erlenmayer flask 125ml and apply 10ml of 10 percent KOH and heated solution. The refluxing mixture was diluted by adding water before the production of precipitation was halted. It was formed by a brownish yellow precipitate. It's required the precipitate mixture to stand overnight. The extracts resulting were obtained by suction pump filtering the precipitate and then re-cristallized by 10-20ml of acetone. We obtained a yellowish white piperine crystal (V. K. Singh et al., 2014).

 

Extraction of capsaicin:

Take 250ml of 95% ethanol in round bottom flask, and add 5-10 boiling balls. Take 20gm of chilli powder and heat the reflux for 2-2.5 hours in soxhlet apparatuses. Subsequently the collected round bottom flask mixture was filtered using suction pump. Then, the filtered solution was condensed by simple distillation to a volume of 15-20ml. Taking the concentrated extract of chili(capsaicin) dissolve in alcohol solution, heating and stirring uniformly, adding a mixed enzyme of lipase and cellulase to the capsacin alcohol solution and performing heat-preservation stringing, adding a ferric chloride solution to a mixed solution heating uniformly stirring and separating a light step, concentrating and drying the distilled capsa.

 

Preparation of emulsion phases:

The oily phase of emulsion was prepared by dissolving span-20 with the necessary quantity of Etodolac in ethanol in light liquid Paraffin. It was combined with piperine and capsaicin as a permeation enhancer. Dissolving tween-20 into distilled water prepared an aqueous process. Methyl paraben was combined with aqueous phase and dissolved in propylene glycol.

 

Preparation of gel:

Precisely weighed quantity of carbopol-940 was taken in a previously dried beaker, adding 10ml of distilled water. It was well combined with regular stirring, using mechanical shaker. Added more distilled water to keep the gel consistent. The pH of the formulation with triethanolamine was changed to 6.0 to 7.0.

 

Formulation of Emulgel:

The oily and aqueous phases were heated to 700şC to 800şC separately, then combined with the continuous stirring and allowed to cool to room temperature. The emulsion obtained was combined with the gelling agent carbopol 940 (or HPMC) in a ratio of 1:1 with a gentle stirring to obtain the formulation of the Fluticasone propionate emulgel and separate formulation prepared as given in Table 8 (M. I. Mohamed et al., 2004 and Rajesh Asija et al., 2015).

 

Evaluation of Emulgel:

Physical characteristic:

The formulated emulgel formulations were visually examined for their pH, colour, homogeneity, purity, grittiness, stiffness and distinction of phases.

 

 

Determination of pH:

The pH of the emulgel formulas had been measured by electronic pH meters. One gram of gel was dissolved in 25ml of purified water, during which the electrode was immersed in gel formulation for 30 minutes until continuous reading was obtained and steady reading was observed. The pH of each formulation was determined in triplicate and the average values were estimated (Jain A et al., 2010).

 

Washability:

Formulations were added to the skin and then manually tested for ease and duration of washing with water.

 

Extrudability study:

The formulations of the emulgel is lined in collapsible metal tubes or collapsible tubes of aluminium. The tubes were pressed to extrude the material, and the formulation extrudability was tested (Gupta GD et al., 1999).

 

Spreadability:

Two standard slides (62) of dimensional glass were picked. The composition of the emulgel which had to be measured for spreadability was put on one of the diapers. The second slide was put over the slide in such a way as to sandwich between them for a length of 6cms the formulation along the slide. The upper slide was coated with 100grams of weight, so that the emulgel formulation was distributed uniformly between the two slides to create a thin layer. The weight was removed, and the emulgel's residual substance adhering to the slides was scraped free. The lower slide was mounted on the equipment plate, and one end of the upper slide was attached to a string on which a basic pulley could be used to apply 20grams of load. The time taken to push 6 cms distance and remove the upper slide was noted Under weight path h from the lower slip. The experiment was repeated, and an average of 6 such determinations were calculated for each emulgel formulation (Sanjay et al., 2007 and Gupta GD et al., 2005).

 

                           m.l

Spreadability = ----------

                               t

 

Where, S = Spreadability (gcm/sec)

m = Weight fastened to the top slide (20grams)

l = Glass Slip Size (6cms).

t = Time consumed is seconds.

 

In-vitro Drug release study:

The experiments on in vitro drug release of the emulgel were conducted on Diffusion cell with egg membrane. It was densely clamped on to one end of the hollow glass tube of the dialysis cell. Emulgel (1gm) was applied to egg membrane surface dialysis. A solution of freshly prepared PBS (pH 7.4) was filled in to the receptor chamber to solubilize the drug. The receiver chamber was filled with magnetic stirrer. The samples (1ml aliquots) were obtained by UV visible spectrophotometer at 274nm for product content at the appropriate time interval test, after adequate dilutions. Total corrections for having the cumulative sum of opioid release were made at each time span. The cumulative amount of drug release over the egg membrane is determined as a function of time. The combined net release of drugs using the standard calibration curve was calculated (V Singla et al., 2012; Snehal P et al., 2013).

 

Details of dissolution testing:

Medium of dissolution: Saline phosphate buffer pH 7.4

Speed: 50rpm

Aliquots taken at every time: 1ml

Temperature: 37±20C

Wavelength: 274nm

 

Stability studies:

The engineered emulgel formulations were prepared; packaged in aluminum collapsible tubes and subjected to 400C/75 percent RH stability studies for a duration of three months as per ICH guidelines. Samples were taken at 1 month intervals and tested for physical appearance, pH, rheological properties, product quality and release of drugs (ICH Guidelines, 2003).

 

RESULTS AND DISCUSSIONS:

Pre-formulation studies:

Solubility (at room temperature)

The solubility of the drug was determined in different solvent was given in Table 2.

 

Table.2: Solubility studies of Etodolac in different solvent

S. No.

Solvent Used

Etodolac

1.

Distilled Water

Insoluble

2.

0.1 N HCl

Slightly Soluble

3.

Ethanol

Soluble

4.

Methanol

Soluble

5.

Chloroform

Slightly soluble

6.

0.1 N NaOH

Soluble

7.

Phosphate Buffer pH 7.4

Soluble

 

It was found that Etodolac was practically insoluble in water, soluble in ethanol and methanol, 0.1 N NaOH and phosphate buffer pH 7.4.

 

Drug excipients compatibility studies:

The possibilities of drug-excipient interactions were investigated by recording the FT- IR spectrum. The FT- IR spectra of the drug and the formulations are shown in figures 4 and 5.

 

Fig. 3: FTIR spectra of Etodolac

 

Fig.4: FTIR Spectra of Formulation

 

It is confirmed that there is no major shifting as well as loss of functional peaks between the spectra of drug and drug loaded Emulgel.

 

Standard calibration curve for Etodolac:

The UV Spectrophotometric method was used to analyze Etodolac. The absorbance of the drug in phosphate buffered saline pH 7.4 with small amount of methanol was measured at a wavelength of 274nm. The results are given in Table 3 and Figure 5.

 

Table.3: Data for calibration curve of Etodolac

S. No.

Concentration (µg/ ml)

Absorbance* at 277 nm

1

2

0.083± 0.0180

2

4

0.200± 0.0314

3

6

0.303± 0.035

4

8

0.409± 0.0396

5

10

0.506± 0.0467

*Mean± SD (n=3)

 

Figure 5: Standard curve of Etodolac in PBS pH 7.4

 

The standard curve of Etodolac in PBS pH 7.4 was linear in 2 to 10µg/ml concentrations, starting from origin. The curve obeys Beer Lambert’s law.

 

Evaluation of Emulgel:

Physical Appearance:

The formulations of Emulgel is white viscous creamy preparation with a smooth homogeneous texture and a shiny feel. Data dealt with in Table 4.

 

Determination of pH:

The pH of the Emulgel formulations was 6.8±0.1 to 6.0 ±0.4, which is below the normal pH range of the skin and does not cause skin discomfort. There has been no substantial improvement in pH values as a function of time for all the formulations. Table 5 below displays the info.


Table.4: Physical parameter of formulation batches

Formulation

Colour

Homogeneity

Consistency

Phase separation

F1

White

Excellent

Excellent

None

F2

White

Excellent

Excellent

None

F3

White

Excellent

Excellent

None

F4

White

Excellent

Excellent

None

F5

White

Excellent

Excellent

None

F6

White

Excellent

Excellent

None

F7

White

Excellent

Excellent

None

F8

White

Excellent

Excellent

None

F9

White

Excellent

Excellent

None


Table.5: Evaluation data of Different Formulations F1-F9 (Mean±S.D.)

Formulation

pH

Viscosity (cps)

Spreadability (gcm/sec)

Extrudability

Washability

Drug Content (% W/W)

F1

6.80± 0.1

4450

14.56±0.21

++

+++

97.727±0.15

F2

6.72± 0.3

4565

13.25±0.36

+

+++

99.12±0.3

F3

6.22± 0.2

4632

16.65±0.56

+++

+++

99.70±0.26

F4

6.65± 0.3

4755

15.45±0.45

+++

+++

99.62±0.36

F5

6.87± 0.5

4898

15.65±0.58

++

++

98.76±0.4

F6

6.45± 0.4

4950

16.45±0.32

++

++

98.45±0.35

F7

6.31± 0.6

4990

14.45±0.12

++

++

99.43±0.5

F8

6.65± 0.6

4865

10.25±0.32

++

++

98.78±0.20

F9

6.02± 0.4

4850

14.45±0.12

+++

+++

99.54±0.47

Excellent: +++, Good: ++, Average: +

 


Rheological study:

The Emulgel with spindle 07 rotated at 50rpm for 10 min. Please note the corresponding reading. This obtained the Emulgel's viscosity. As polymer concentration increases, the viscosity of the formulations increases. The specifics are shown in Table 5.

 

Spreadability:

The Emulgel's spreadability was decreased with the polymer concentration increases. The spreadability is very significant because it demonstrates Emulgel 's action comes out of the tunnel. The details are shown in Table 5.

 

Extrudability:

Upon formulating them, the gels had been poured into collapsible cylinders. The extrudability of the formulation was tested, and the findings were summarized in Table 5.

 

Drug content:

Analysis of drug composition was performed to assess the amount of the medication contained in the specific quantity of the formulation. Spectrophotometrically, Formulated Emulgel was measured at 277nm. The specifics are shown in Table 5.

 

In- vitro release study:

Study of in-vitro drug release: Ethodolac release from the Emulgel varied according to polymer concentration. The release of the drugs from its formulation of emulsified gel may be classified in the following descending order : F4 > F2 > F5 > F1 > F3 > F6 > F8 > F7 > F9. Gradual rise in the volume of drug spread by Formulation membrane ascribed to a steady decline in polymer concentration. It's been over and done with that, if we increase polymer concentration, drug diffusion through the membrane also decreases. Spectrophotometrically, the drug content of the prepared emulgel was estimated to be 277nm. The findings were within official limits, and the total percentage of drug release profile of all batches of formulation was shown in Table 6 and Fig. 6.

 

The average product release ranged from 73.79 to 49.08 percent at 8 hours in all formulation. Relative to other formulations, the average release was found to be 73.79 per cent in F4 formulation.


 

Table.6: In Vitro Cumulative %Drug Release Formulation F1-F9

Time in (Hrs)

Cumulative % Drug Release (% w/w)

F1

F2

F3

F4

F5

F6

F7

F8

F9

0

0

0

0

0

0

0

0

0

0

1

8.43±0.14

10.71±0.10

13.21±0.03

4.15±0.01

4.92±0.09

7.36±0.12

3.67±0.05

9.93±0.07

6.23±0.11

2

16.09±0.27

21.66±0.52

29.43±0.08

25.35±0.36

14.75±2.63

14.07±0.08

13.24±0.45

21.46±0.11

14.46±0.09

3

25.38±1.04

26.47±0.34

36.12±0.23

31.91±0.47

23.37±0.33

22.87±1.23

16.34±0.13

26.12±1.34

20.02±0.01

4

31.53±0.45

33.07±1.23

42.27±0.12

38.30±0.89

29.5±1.96

29.45±0.24

21.49±0.26

33.08±1.23

27.56±0.23

5

38.59±0.17

41.75±1.34

51.19±0.24

44.73±0.11

34.37±0.25

33.63±0.17

27.37±0.23

38.98±0.43

32.22±0.52

6

43.52±0.31

47.97±0.19

56.64±0.23

52.62±0.11

40.56±0.28

38.64±2.10

34.93±0.23

43.16±0.31

38.85±0.14

7

47.94±0.34

54.79±0.26

60.32±0.23

54.48±0.69

47.37±1.50

46.32±0.13

41.29±0.32

47.59±0.23

45.19±1.31

8

65.38±0.23

70.11±1.29

62.78±2.28

73.79±0.98

68.90±1.23

59.97±2.15

52.67±0.14

56.12±0.27

49.08±0.42

 

Fig.6: In Vitro Cumulative % Drug Release Different Formulation F1-F9

 

SUMMARY AND CONCLUSION:

In summary, the results of this research establish a new and useful approach in the design of a formulation 's oil phase where the active ingredient needs to be dissolved in the oil phase and Emulgel system developed. In addition, the use of Emulgels for topical delivery of hydrophobic drugs has been found to be better at achieving a higher concentration of drugs across the skin barrier over a longer period of time compared with gels.

 

ACKNOWLEDGEMENT:

I am thankful to the management of Sambhunath Institute of Pharmacy, Praygraj for providing best lab facilities necessary for completion of my research

 

CONFLICT OF INTEREST:

The authors declared no conflict of interest.

 

REFERENCES:

1.      Alfonso R. Gennaro, Remington: The Science and Practice of Pharmacy, 17th edition, Mack Publishing Company; 1985 Chapter No. 11 Pharmaceutical and Medicinal agents, P. 1644-1661.

2.      Bacchi, S., et al., Clinical Pharmacology of Non-Steroidal Anti-Inflammatory Drugs: A Review. Vol. 11. 2012. 52-64.

3.      Carstensen J.T., 1996. Preformulation. In: Banker G.S., Rhodes C.T., Editors. Modern Pharmaceutics. 3rd edition. New York: Marcel Dekker; Vol. 72 Drug and The Pharmaceutical Sciences, pp. 213-37.

4.      Chein YW. Novel drug delivery systems: Fundamentals, development, concepts and biomedical application. Marcel Dekker, New York, 1981; P. 139-217, 301-380.

5.      Davis, J.S., et al., Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic. Open heart, 2017. 4(1): p. e000550.

6.      Dickson, D., A double-blind evaluation of topical piroxicam gel with oral ibuprofen in osteoarthritis of the knee. Curr Ther Res., 1991. 49: p. 199-207.

7.      Gopinath R., Naidu R.A.S., 2011. Pharmaceutical Preformulation studies – current review. Int J Pharm Biological Arc, Vol. 2, Issue 5, pp. 1391-1400

8.      Gupta GD, Gaud RS. Release rate of Nimesulide from different gellants. Ind J Pharm Sci 1999; 61: 229-234.

9.      Gupta GD, Gaud RS. Release rate of Tenoxicam from Acrypol gel. The Indian Pharmacist 2005; 69- 76.

10.   Margaret N, Mutimer CR, Hill JA, Murray E. Modern ointment base technology comparative evaluation of bases. J American Pharm Association 1956; 4: 212- 217.

11.   Nair R, Sevukarajan M, Mohammed B, and Kumar J (2010). Formulation of Microemulsion based vaginal gel in-vitro and in-vivo evaluation. Der Pharmacia Lettre, 2: 99-105.

12.   P. Sridhara Babu, M. Guravaiah, I. Hatti, K. Srikanth. Qualitative analysis of capsaicin from chillies and chilli powder by H.P.L.C method. Int. J. Curr. Res. Chem. Pharma. Sci. 2014, 1(6): 184-194.

13.   Patel J, Trivedi J, Chudhary S (2014). Formulation and evaluation of diacerein emulgel for psoriatic arthritis. Int J Pharm Res Bio-Sci, 3: 625-638.

14.   Prajapati MK., Patel MR., Patel KR., Patel NM. Emulgel: a novel Approach to topical drug delivery. International Journal Univ Pharm Bio Sci. 2013; 2(1): 134-148

15.   Rajesh Asija, Nitin Nama, Deepak Sharma Development and evaluation of novel Fluticasone Propionate Emulgel for topical drug delivery. Journal of Chemical and Pharmaceutical Research, 2015, 7(2): 772-780.

16.   Ricciotti, E. and G.A. Fitz Gerald, Prostaglandins and Inflammation. Arteriosclerosis, thrombosis, and vascular biology, 2011. 31(5): p. 986-1000.

17.   Robinson RJ, Lee VH. Controlled Drug Delivery: Fundamental and Application. 2nd edition, Marcel Dekker, New York; 1987: Chapter-1”Influence of drug properties and routes of drug administration on the design of sustained and controlled release systems” P 4-61.

18.   Sanjay, Jain BD, Padsalg A, Patel K, Mokale V. Formulation development and evaluation of fluconazole gel in various polymer bases. Asn J Pharm 2007; 1: 63- 68.

19.   SB Shirsand, MS Para, D Nagendrakumar, KM Kanani and D Keerthy. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system. Int J Pharm Investig. 2012; 2(4); 201- 207.

20.   Snehal P. Mulye, Kiran A. Wadkar and Manish S. Kondawar Formulation development and evaluation of Indomethacin emulgel. Der Pharmacia Sinica, 2013, 4(5): 31-45

21.   Tadicherla, S. and Berman, B. (2006). Percutaneous dermal drug delivery for local pain control. Ther Clin Risk Manag. 2(1): 99-113.

22.   Technologie 10(3): 30-46.

23.   Tushar L., Akhilesh D., Prabhakara P., Kamath J.V., 2012. Preformulation studies of controlled/sustained release formulations: an review. Int Res J Pharmacy, Vol. 3, Issue 5, pp. 95-99.

24.   V Singla; S Saini; AC Rana, Emulgel: a new platform for topical drug delivery. Int Pharma Sci., 2012, 2(3), 36-44.

25.   V. K. Singh, V. K. Mishra, J. K. Maurya, S. K. Singh, A. Mishra. Formulation and Evaluation of Cephalexin Monohydrate Reconstitutional Oral Suspension with Piperine and Their Antibacterial activity. World Journal of Pharmaceutical Research, 2014, 3(5), 821-831.

26.   Wadke P.A., Jacobson S., 1980. Preformulation Testing In: Liberman H.A. and Lachman L., Editors. Pharmaceutical Dosage Forms-Tablets, Vol-I, New York: Marcel Dekker, pp. 1-42.

27.   Wallace, J.L., et al., NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2. Gastroenterology, 2000. 119(3): p. 706-14.

28.   Walters KA. Dermatological and transdermal formulation. Florida CRC Press. 2002; ( 403): 323-327.

29.   Walters, K. A. (1986). Percutaneous absorption and transdermal therapie. Pharm.

30.   Whittle, B.J., Gastrointestinal effects of nonsteroidal anti-inflammatory drugs. Fundam Clin Pharmacol, 2003. 17(3): p. 301-13.

31.   Woodford, R. and Barry, B. W. (1986). Penetration enhancers and the percutaneous absorption of drugs: an update. J Toxicol Cut Ocular Toxicol. 5: 167-77

 

 

 

Received on 25.08.2020           Modified on 27.09.2020

Accepted on 23.10.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2021; 14(9):4868-4874.

DOI: 10.52711/0974-360X.2021.00846