Formulation and Characterization of Resorcinol Peel

Prerana Sahu¹, Anjali¹, Stuti Mishra¹, Gyanesh Kumar Sahu¹, Harish Sharma1, Chanchal Deep Kaur²

¹Shri Shankaracharya Group of Institution, Faculty of Pharmacy, Junwani, Bhilai (C.G.)

^2.Shri Rawatpura Sarkar Institute of Pharmacy, Kumhari (C.G.)

*Corresponding Author E-mail: preranasahu06.ps@gmail.com, gyanesh.sahu@rediffmail.com

ABSTRACT:

Acne is a chronic, inflammatory skin condition that causes spots and pimples, especially on the face, shoulders, back, neck, chest, and upper arms. It occurs when your hair follicles become plugged with oil and dead skin cells. The main objective of this study was to prepare the Resorcinol peel mask for the treatment of acne and toned skin. The resorcinol chemical peel mask can give you smoother, more even toned skin not just on your face, but neck, chest and hands. Gels are evaluated by following parameters such as pH, homogeneity, grittiness drug content, viscosity, spreadability, extrudability, skin irritation studies, in-vitro release, in Stability. This study is further aimed to analyze, concentration of drug reaching into the skin and to study its effect in treatment of acne

KEYWORDS: Resorcinol peel, Acne, Toned skin.

INTRODUCTION:

Acne as an inflammatory condition is driven by multiple factors, including hormonal deregulation.^(1)(52)Whiteheads, blackheads, pimples, cysts and nodules are all types of acne. It is commonly occurred during puberty, when the sebaceous glands activate, but it can occur at any age. It is not dangerous, but it can leave little skin scars. The glands produce oil which are stimulated by male hormones produced by the adrenal glands in both males and females. The resulting appearance may lead to harmful effects such as anxiety, reduced self-esteem and, in extreme cases, depression or thoughts of suicide.^(2)(53)(54)

Clinically, acne is graded according to the types of lesions present: open and closed comedones, inflammatory papules, pustules, cysts, nodules, and even scarring may be seen in various forms of acne. The degree to which both active acne and scars from previous acne may cause psychologic or emotional harm varies from patient to patient and may or may not correlate with clinical severity.

Evidence suggests that the impact of acne on a patient’s psychologic and emotional well-being is comparable with that of systemic disease processes such as diabetes, asthma, arthritis, and epilepsy.^(3)(51)

SYMPTOMS OF ACNE:

Acne signs and symptoms vary depending on the severity of your condition:

· Whiteheads (closed plugged pores)

· Blackheads (open plugged pores)

· Small red, tender bumps (papules)

· Pimples (pustules), which are papules with pus at their tips

· Large, solid, painful lumps beneath the surface of the skin (nodules)

· Painful, pus-filled lumps beneath the surface of the skin (cystic lesions)

Nomenclature Of Acne:^(4)(50)

The three generally types of acne are: acne vulgaris, acne rosacea and acne inversa. All are caused by a disorder cantered on the structure usually called the pilosebaceous apparatus, so named because of its two products, hair and sebum.

Acne Vulgaris:

Vulgaris is a latin word, an adjective that means common. Acne vulgaris is an inflammatory disorder of pilosebaceous unit, which runs a chronic course and it is self-limiting. Acne vulgaris is triggered by Propionibacterium acnes in adolescence, under the influence of normal circulating dehydroepiandrosterone (DHEA). It is a very common skin disorder which can present with inflammatory and non-inflammatory lesions chiefly on the face but can also occur on the upper arms, trunk, and back.^(4)(5)(6)(7)

Fig 1: Nomencluture of acne

Fig.2 Acne Vulgaris

Acne Rosacae:

Classic acne rosacea is a variant of the acnes that shows up on the curved surfaces of the face. It is made up of blemishes centered on the openings of the follicular units of individuals FPSUs. There are little raised bumps (folliculopapules) and very small pustules (folliculopustles).

Fig 3. Acne Rosacae

These little bumps and pustules are the acne and they appear on a rosy red background, the “rosacea”. It is important to understand that acne rosacea actually has three separate components on the face. The first is the pimply acne, the second is the background redness and the third is a thickening of the skin.^(4)(49)

Acne Inversa:

Acne inversa is a recurrent, suppurative disease manifested by abscesses, fistulas, and scarring. Once considered to be a disease of the apocrine glands, it is actually a defect of follicular epithelium. Thus, the term hidradenitissuppurativa is a misnomer and should be abandoned. In cases of familial acne inversa, the pattern of transmission and number of affected individuals are consistent with autosomal dominant inheritance. Aetiological factors such as hyperandrogenism, obesity, smoking and chemical irritants are not consistently associated with the affection. Bacterial involvement is not a primary event in acne inversa, but is secondary to the disease process. Potential complications include dermal contraction, local or systemic infection due to the spread of microorganisms, systemic amyloidosis, arthropathy, and squamous cell carcinoma.⁽⁹⁾

Fig 4.- Acne Inversa in a cheeks of a female

Acne Classification:(10)

Acne has been classified into the following categories.

Grade I (Comedonal acne) consists of comedones only; less than about 10 on the face, none on the trunk, no scarring and noninflammatory in nature.

Grade II (Papular acne) is described by 10-25 papules on the face and trunk with mild scarring and the presence of inflammatory lesions, less than 5 mm in diameter.

Grade III (Pustular acne) consists of more than 25 pustules with moderate scarring.

Grade IV (Severe or persistent pustulocystic acne) consists of nodules or cysts with extensive scarring and

inflammatory lesions over 5 mm in diameter. Also, recalcitrant severe cystic acne characterized with extensive nodules and/or cysts.

Resorcinol:

It is a crystalline compound originally obtained from galbanum resin, used in the production of dyes, resins, and cosmetics. Resorcinol (or resorcin) is an organic compound with the formula C₆H₂(OH)₂. It is one of three isomeric benzenediols, the 1, 3-isomer (or meta-isomer). It is a white, water-soluble solid.⁽¹⁰⁾Resorcinol is produced in several steps from benzene, starting with dialkylation with propylene to give 1, 3-diisopropylbenzene. Oxidation and Hock rearrangement of this disubstitutedarene gives acetone and resorcinol.^(12)(46)Resorcinol crystallizes from benzene as colorless needles that are readily soluble in water, alcohol, and ether, but insoluble in chloroform and carbon disulfide. Resorcinol is a phenol derivative. It has a pKa of 9.32 and is soluble in water, ether and alcohol.^(11)(44)Resorcinol is used at concentrations of 10–50% for chemical peeling and induces a frosting pattern.^(11)(45)It is used in the treatment of acne, acne scars, hidradenitissuppurativa nodules and melisma^(12)(42)(43)

Chemical Peel:

A chemical peel is an acidic solution, which is applied to the affected parts of your skin. On penetrating the skin, the solution destroys dead skin, unclogs pores and makes way for new skin to regenerate. The acne blemishes and scars disappear. Peeling agents may be divided into superficial, medium‐depth and deep subtypes based on the depth of their penetration. They may be used alone or in combination with other cosmetic procedures for cutaneous aesthetic enhancement.^(13)(38)(39)

Table 1 :R_xResorcinol peel formulation:^(9)(13)(40)

Resorcinol	3g
Salicylic acid	2g
Lactic acid 88%	4.6g
Alcohol USP	50ml
Purified water qs	100ml

Method of Preparation(10)(15):

1 Calculate the required quantity of each ingredient for the total amount to be prepared.

2 Accurately weigh/measure each ingredient.

3 Dissolve the resorcinol in the purified water.

4 Dissolve the salicylic acid in the alcohol, followed by the lactic acid and mix well.

5 Add the two solutions together.

6 Add sufficient purified water to volume and mix well.

7 Package in an amber container and label.

STABILITY:

A beyond-use date of 6 months can be used for this formulation.^{(14)(36)(46)(47)}

Application:

The application technique varies according to the peeling agent used. Liquid products may be applied with a brush, cotton tip applicator or cotton or gauze swab. A wooden spatula is used to apply gels. Chemical peeling should start on areas of thicker skin. The forehead, cheeks, nose and chin are treated first, followed by the perioral and periorbital skin. The peeling agent should be applied in an upward direction with firm even strokes and extended beyond the vermillion border and into the oral commissures. Care should be taken to avoid overlapping brush strokes and skipping areas. A feathering technique should be employed at the edge of the treatment field to avoid sharp demarcation lines. In areas of deep wrinkling the clinician should stretch the skin to prevent pooling of the peeling agent.^(15)(37)(41)

Fig 4: Aesthetic units of the face.

How to apply:^(16)(35) Peeling Technique

· The skin is scrubbed with alcoholor acetone

· The gel is spread over the face.

· Start on forehead and Continue on the cheeks

· Then the nose and the chin up to 1 cm below the mandibular margin

· The patient is instructed to keep the eyes and the mouth closed to prevent accidents pillage

· The gel is kept for 15-20minutes.

· The paste is removed with water.

· After the removal of the paste the skin is white but turns to pink within 2 to 3 h.

Advantages:^(17)(33)(34)

· Easy to perform

· Uniformity of application and penetration

· Effective especially in acne, post-inflammatory hyperpigmentation and melasma

· Not painful (the burning sensation during the peeling is usually mild)

Characterization:

After getting best formulae based on resorcinol, salicylic acid and lactic acid ratio, it was further studied for its characterization such as pH value, viscosity, physical appearance, homogeneity, spreadabibility, grittiness, etc.

Physical appearance:

The physical appearance test of peel is done by observing it through sensory organ for determining its color, odour, appearance.

pH value:

pH values were measured at room temperature by using pH meter of model no. Me-962P. Readings were taken for each sample.

Viscosity measurement:

Viscosity of the selected formulation was measured by using the Brookfield viscometer of model no. WDV-8 at room temperature. This viscometer is used for determining the viscosity of gels & oils. The value of viscosity is expressed in centipoise. Centipoise is defunct unit of viscosity measurement.^{(18)(19)(29)(30)}Firstly the spindle number of Brookfield viscometer was found out by trial and error method; after that sample was poured in the beaker and spindle was dipped into it to find out the viscosity at different RPM. The value of torque and viscosity was then recorded.^{(20)(21)(28)(37)}

Homogeneity:

Homogeneity is defined as the quality or state of being of a similar kind or of having a uniform structure or composition throughout.

Spreadability test:^{(22)(23)(31)(32)}

Gel base should spread easily without too much drag and should not produce greater friction in the rubbing process. Spreadability was calculated using the spreadability apparatus made of wooden board with scale and two glass slides having two pans on both sides mounted on a pulley.

Excess sample was placed between the two glass slides and 100 g weight was placed on the glass slide for 5 min to compress the sample to a uniform thickness. Weight (250 g) was added to the pan. The time in seconds required to separate the two slides was taken as a measure of spreadability.

S = m * l/t

m – Weight tied on upper slide

l – Length of glass slide

t – Time in s

Determination of release rate using franz diffusion cell:

The Vertical Franz Diffusion Cell is a simple, reproducible test for measuring the in vitro drug release from creams, ointments and gels. The Franz Cell consists of two primary chambers separated by a membrane. The test product is applied to the membrane via the top chamber- donor compartment. The bottom chamber- receptor compartment contains fluid from which samples are taken at regular intervals for analysis. This testing determines the amount of active drug that has permeated the membrane at each time point. Franz Cells are a widely used methodology to evaluate in vitro drug permeation which has advantages, such as (i) few handling of tissues, (ii) no continuous sample collecting and (iii) low amount of drug required for analysis. With the rise of personalized medicine, it is necessary to develop various pharmaceutical dosage forms for the same active molecule allowing the variability of administration and dosage.^{(24)(25)(26)(27)(55)}

RESULTS AND DISCUSSION:

1. Physical appearance:

The physical appearance test of peel is done by observing it through sensory organ and following observation is made.

Fig 5: Resorcinol peel sample

Table 2: Organoleptic properties

Color	Milky white
Odour	Aromatic
Appearance	Thick less viscous

2. pH value:

pH values of the sample is measured by using pH meter. The graph indicates that all the resulted pH values are in range between 4.2–5.4. These values indicate that emulsion is suitable for topical administration.

Table 3: pH value of Formulation

S. No	Sample	pH
1	p	4.2
2	q	4.6
3	r	4.5
4	s	5.2

Fig 6: Graphical representation of pH values of samples

3. Spreadability:

The results of the spreadability of the peel is given in the table below:

Table 4: Spreadability

S. No	Sample	Spreadability (g.cm/sec)
1	p	10.2
2	q	9.2
3	r	8.7
4	s	7.9

4. Homogeneity:

It is tested for their appearance and presence of any clumps, flocculates or aggregates.

Table 5: Homogeneity

S. No.	Sample	Homogeneity
1	P	Flocculates
2	Q	Flocculates
3	R	Aggregates
4	S	Aggregates

5. Franz Diffusion Cell Release Rate:

Fig 7: Franz diffusion cell apparatus with skin

The results of the absorption by the UV spectroscopy by analyzing the concentration of absorption with different time intervals is given below:

Fig 8: UV spectroscopy

Table 6: Absorption rate

S. No	Time	Absorption
1	10min	0.301
2	20min	0.426
3	30min	0.501
4	60min	0.714
5	90min	0.919

6.Viscosity measurement:

Table 6: Result recorded for viscosity measurement

S. No.	Sample	Viscosity (Cp)
1	P	11354
2	Q	12345
3	R	13769
4	S	14568

Fig 9: Graphical representation of viscosity of different samples

7. Stability Test:

After 7 days

Table 7: Stability data after 7 days

S. No.	Sample	TEMPERATURE (⁰C)
		14-21	21-25	25-30
1	P	Stable	Stable	Stable
2	Q	Stable	Stable	Stable
3	R	Stable	Not stable	Not stable
4	S	Stable	Stable	Not stable

After 14 days:

Table 8: Stability data after 14 days

S. No.	Sample	TEMPERATURE (⁰C)
		14-21	21-25	25-30
1	P	Stable	Stable	Stable
2	Q	Stable	Stable	Stable
3	R	Stable	Not stable	Not stable
4	S	Stable	Stable	Not stable

After 21 days:

Table 9: Stability data after 21 days

S. No.	Sample	TEMPERATURE (⁰C)
		14-21	21-25	25-30
1	P	Stable	Stable	Not stable
2	Q	Stable	Stable	Stable
3	R	Not stable	Not stable	Not stable
4	S	Stable	Nonstable	Not stable

After 28 days:

Table 10: Stability data after 28 days

S. No.	Sample	TEMPERATURE (°C)
		14-21	21-25	25-30
1	P	Stable	Not stable	Not stable
2	Q	Stable	Not stable	Not stable
3	R	Not stable	Not stable	Not stable
4	S	Not stable	Not stable	Not stable

DISCUSSION:

The important criterion for selection of components for peel formulation is their compatibility with other component. It has been demonstrated that only few excipients combinations lead to effective peel formulations.

Maintaining the ph value is significant for determining the stability of the peel because change in ph specifies the occurrence of chemical reactions in the formulation.

The resulting ph of sample p, q, r, s is found as 4.2, 4.j5, 4.6 and 5.2 respectively. The sample q with greater viscosity is found to be more stable.

ACKNOWLEDGEMENT:

Authors want to acknowledge the facilities provided by the Shri Shankracharya Technical Campus, Faculty of Pharmaceutical sciences, Junwani, Bhilai, Chhattisgarh. The authors also grateful to Mr. Gyanesh Sahu for his help to complete work in stipulated period of time.

CONCLUSION:

This study is further aimed to perform in vivo studies for analyzing the concentration of resorcinol reaching into the skin and to study its effect, which will help to reduce the dose of resorcinol peel and to make its novel dosage form for treatment of Acne.

REFERENCES:

1. Zaenglein A, Pathy A, Schlosser B, et al. Guidelines of care for the treatment of acne vulgaris. J Am Acad Dermatol 2016; 74(5):945–73.

2. Goodman, G (July 2006). "Acne and acne scarring–the case for active and early intervention". Australian Family Physician (Review). 35 (7): 503–4. PMID 16820822. Archived from the original on 21 April 2013.

3. Mallon E, Newton JN, Klassen A, Stewart-Brown SL, Ryan TJ, Finlay AY. The quality of life in acne: a comparison with general medical conditions using generic questionnaires. Br J Dermatol 1999; 140:672-6.

4. Danby, F. William. Acne: causes and practical management. John Wiley & Sons, 2015.

5. Yan HM, Zhao HJ, Guo DY, Zhu PQ, Zhang CL, Jiang W. Gut microbiota alterations in moderate to severe acne vulgaris patients. J. Dermatol. 2018 Oct; 45(10):1166-1171.

6. Juhl CR, Bergholdt HKM, Miller IM, Jemec GBE, Kanters JK, Ellervik C. Dairy Intake and Acne Vulgaris: A Systematic Review and Meta-Analysis of 78, 529 Children, Adolescents, and Young Adults. Nutrients. 2018 Aug 09; 10(8).

7. George RM, Sridharan R. Factors Aggravating or Precipitating Acne in Indian Adults: A Hospital-Based Study of 110 Cases. Indian J Dermatol. 2018 Jul-Aug; 63(4):328-331.

8. Jansen, T., P. Altmeyer, and G. Plewig. "Acne inversa (alias hidradenitissuppurativa)." Journal of the European Academy of Dermatology and Venereology 15.6 (2001): 532-540.

9. Spraycar M. Ed. Stedman's Medical Dictionary, 26th ed.Baltimore, Williams & Wilkins. 1995, p 16.

10. K. W. Schmiedel, D. Decker (2012), "Resorcinol", Ullmann's Encyclopedia of Industrial Chemistry, Weinheim: Wiley-VCH, doi:10.1002/14356007.a23111.pub2CS1 maint: Uses authors parameter

11. Zakopoulou N, Kontochristopoulos G. Superficial chemical peels. J. Cosmet. Dermatol.2006; 5: 246–53.

12. Boer J, Jemec GB. Resorcinol peels as a possible self‐treatment of painful nodules in hidradenitissuppurativa. Clin. Exp. Dermatol. 2010; 35: 36–40.

13. Collins, PS. The chemical peel. Clin. Dermatol. 1987; 5: 57– 74. Crossref CAS PubMed Web of Science®Google Scholar

14. Rendon M, Berson DS, Cohen JL, Roberts WE, Starker I, Wang B, Evidence and Considerations in the Application of Chemical Peels in Skin Disorders and Aesthetic Resurfacing. 2018. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921757/. Accessed March 2, 2018

15. Khunger N, Force IT. Standard guidelines of care for chemical peels. Indian J. Dermatol. Venereol. Leprol. 2008; 74 (Suppl.): S5–12

16. US Pharmacopeial Convention, Inc. United States Pharmacopeia 24/National Formulary 19. Rockville, MD: US Pharmacopeial Convention, Inc.; 2001, pp 2053-2057.

17. Ghersetich I, Brazzini B, Lotti T (2003) Chemical peeling. In: Lotti TM, Katsambas AD (eds) European handbook of dermatological treatments, 2nd ed. Springer, Berlin, Heidelberg, New York.

18. Rajesh Yadav, Nita. Yadav, Murli Dhar Kharya. Steroid Chemistry and Steroid Hormone Action: A Review. Asian J. Research Chem. 7(11): November, 2014; Page 964-969.

19. Sandeep Pokharia. An Atoms-in-molecules (AIM) interpretation of organotin-peptide system: I. Di-n-butyltin (IV) derivative of glycyltryptophane. Asian J. Research Chem. 2017; 10(2):115-118.

20. Gangadhara MM, Dinesha R, Satish Kumar Murari. A non-cytotoxic pseudo peptide KL1 with potent antioxidant activity. Asian J. Research Chem. 2017; 10(2):127-130.

21. D. M. Suyoga Vardhan, H. K. Kumara, H. Pavan Kumar, D. Channe Gowda. Urea and Thiourea Derivatives of Dipeptides Conjugated Piperazine Analogue as A New Class of AGE’s Inhibitors: Synthesis and Molecular Docking Studies. Asian J. Research Chem. 2017; 10(4):459-469.

22. Lachman L, Liberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 3rd ed. Mumbai: Varghese Publishing House; 1987. pp. 534–63.

23. Gupta GD, Gaud RS. Practical Microbiology. 3rd ed. Pune: Nirali Prakashan; 2004. pp. 40–4.

24. Khengar R.H., Jones S.A., Turner R.B., Forbes B., Brown M.B. Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers. Pharm. Res. 2007; 24:2207–2212.

25. Simon A., Amaro M.I., Healy A.M., Cabral L.M., de Sousa V.P. Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation. Int. J. Pharm. 2016; 512:234–241.

26. Kulkarni K.N., Datta-Gupta A. Estimating Relative Permeability From Production Data: A Streamline Approach. SPE J. 2000; 5:402–411

27. Tripathi S, Sahu UM, Meshram J, Kumari R, Tripathi D.K., Ajazuddin, Alexander A, Sharma H, Sahu G; Reasearch article, Formulation and characterization of Virgin Coconut Oil Emulsion (VCOE) for treatment of Alzheimer’s disease; Research Journal of Pharmaceutical Dosage Forms and Technology. 10(2): April- June, 2018

28. Kader N S A, Ansari N, Bharti R, Mandavi N, Sahu G, Jha A K, Sharma H; Review article; Novel Approaches for Colloidal Drug Delivery System: Nanoemulsion; Research Journal of Pharmaceutical Dosage Forms and Technology. 10(4): October- December, 2018

29. Sharma H, Dapurkar V K, Rai G, Sahu G K; Research article; Microemulsions for the Topical Administration of 5- Fluorouracil: Preparation and Evaluation; Research J. Pharm. and Tech. 5(8): August 2012

30. Mandavi N, Ansari N, Barti R, Kader N S A, Sahu G, Sharma H; Review article,

31. Microemulsion: A Potential Novel Drug Delivery System; Research Journal of Pharmaceutical Dosage Forms and Technology. 10(4): October- December, 2018

32. Sahu S k, Ajazuddin, BanjareT, Gupta S, Bhandarkar A, Sahu H, Diwedi S.D, Sahu P, Agrawal P, Yadav P, Bhatt A, Sahu K, Dewangan D, Thapa H, Deepika, Sahu G, Sharma M, Tripathi D.K., Alexander A; Research article; Formulation and evaluation of orodispersible tablet of montelukast sodium; Research J. Pharm. and Tech. 11(3): March 2018

33. Sahu g, Sharma H, Dapurkar V, Rai G; Research article; Development and Evaluation of Methotraxate Loaded BSA Microspheres; Int. Res J Pharm. App Sci., 2012; 2(5): 9-12

34. Sahu G, Sharma H, Kaur C.D., Review article; A Novel Approach of Magnetic Modulated Microspheres; Asian J. Pharm. Res. 2013; Vol. 3: Issue 4, Pg 220-224

35. Sahu G, Sharma H, Kaur C.D., Review article; Evolving concepts and targeting of arthritis; World Journal of Pharmaceutical Research, Vol 3, Issue 4, 2014. 1960

36. Sharma H, Sahu G.K., Dapurkar V; Review article; An overview of new drug delivery system: Microemulsion; Int. Res J Pharm. App Sci., 2012; 2(5): 1-8

37. Tripathi S, Sahu U, Meshram J, Kumari R, Tripathi D.K, Ajazuddin, Alexander A, Sharma H, Sahu G. Research article Formulation and characterization of virgin coconut oil emulsion (vcoe) for treatment of alzheimer’s disease. Research Journal of Pharmaceutical Dosage Forms and Technology. Issue-02 April- June, 2018; 1-6.

38. Gupta S, Sahu G, Sharma M, Chandrakar S, Sahu V, Sharma G, Dewangan K, SolankiH, Majumdar M, Tripathi D.K, Alexander A, Ajazuddin. Research article; Preparation and Optimization of floating microbeads of ciprofloxacin HCl. Research J. Pharm. and Tech. 9(7): July 2016; 1-5.

39. Dapurkar V, Sahu G, Sharma H, Meshram S, Rai G. Research Article Anti-Arthritic Activity of Roots Extract of Boerhaavia Diffusain Adjuvant Induced Arthritis Rats. Scholars Academic Journal of Pharmacy (SAJP). Sch. Acad. J. Pharm., 2013; 2(2):107-109.

40. Roy A, Wahane A, Karankal S, Sharma P, Khutel D, Singh O, Shardul V, Pitamber, Sabha N, Dewangan J, Dewangan A, Jangde A, Rani C, Sahu T, Tripathi D. K., Agrawal M, Ajazuddin, Sahu G, Alexander A. REVIEW ARTICLE Pharmaceutical Aspects on the Formulations of Hydrogel: An Update. Research Journal of Pharmaceutical Dosage Forms and Technology.January- March, 2018; 1-6.

41. Sahu G, Sharma H, Gupta A, Kaur C. Review Article Advancements in Microemulsion Based Drug Delivery Systems for Better Therapeutic Effects. International Journal of Pharmaceutical Sciences and Developmental Research.31 August, 2015; 1-8

42. Behzadmehr R, Parooei F, Salarzaei M. Varices of the Round Ligament with Thrombosis (A Review Article and Report). Research Journal of Pharmacy and Technology. 2018; 11(1):405-6.

43. Ulaganathan G, Senthil kumar R. Citations and Self citations of Indian Authors in Pharmacy Journals: A Study Based on Indian Citation Index. Journal of Advanced Research in Pharmaceutical Sciences & Pharmacology Interventions. 2017; 1(1):14-20.

44. Sharma D, Soni M, Kumar S, Gupta GD. Solubility enhancement–eminent role in poorly soluble drugs. Research Journal of Pharmacy and Technology. 2009; 2(2):220-4.

45. Rosman A, Simon R. Flow heterogeneity in reservoir rocks. Journal of Petroleum Technology. 1976 Dec 1; 28(12):1-427.

46. Manokaran S, Jaswanth A, Sengottuvelu S, Nandhakumar J, Duraisamy R, Karthikeyan D, Mallegaswari R. Hepatoprotective activity of Aervalanata Linn. Against paracetamol induced hepatotoxicity in rats. Research journal of pharmacy and technology. 2008; 1(4):398-400.

47. Chanda R, Mahapatro SK, Mitra T, Roy A, Bahadur S. Development of Oral Mucoadhesive Tablets of Terbutaline Sulphate Using Some Natural Materials Extracted from Albelmoschusesculeatus and Tamarindusindica. Research Journal of Pharmacy and Technology. 2008; 1(1):46-51.

48. Alam N, Agrawal OP, Alam P, Agrawal S, Kaushik M, Dhari JS, Sharma OP. Natural Immunoenhancers. Research Journal of Pharmacy and Technology. 2011; 4(10):1526-32.

49. Kumar L. An Overview on Preparation and Evaluation of Microparticulated Intra-Vaginal Gel. Research Journal of Pharmacy and Technology. 2009; 2(1):48-51.

50. Al-Snafi AE. Chemical constituents and pharmacological importance of Agropyronrepens–A review. Research Journal of Pharmacology and Toxicology. 2015; 1(2):37-41.

51. Udgirkar DB, Hiremath SN, Rao KS, Pawar D. Formulation and in-vitro evaluation of buccoadhesive tablets containing ketoconazole inclusion complex with β-cyclodextrin. Research Journal of Pharmacy and Technology. 2009; 2(2):396-404.

52. Shirsat MK, Gupta SK, Vaya R, Dwivedi J, Singhvi IJ, Ashawat MS, Mahatma OP. Chemometric Study of Herbal Extracts of Calotropisgigantea Linn. By FT-IR Spectroscopy. Research Journal of Pharmacy and Technology. 2011; 4(7):1052-4.

53. Ekka NR, Namdeo KP, Samal PK. Standardization strategies for herbal drugs-An overview. Research Journal of Pharmacy and Technology. 2008; 1(4):310-2.

54. Alagusundaram M, Chetty CM, Umasankari K, Anitha P, Gnanprakash K, Dhachinamoorthi D. Buccal Drug Delivery System–An Overview. Research Journal of Pharmacy and Technology. 2009; 2(4):653-63.

55. Shankar NB, Kumar NU, Balakrishna PK, Kumar RP. Preparation and in vitro evaluation of lamivudine entrapped MOI microspheres for oral administration. Research Journal of Pharmacy and Technology. 2008; 1(4):437-40.

56. Janati A, Amini A, Adham D, Naseriasl M. Referral system in Iran's health sector and world's leading countries. Research Journal of Pharmacy and Technology. 2017 Jun 1; 10(6):1597-602.

57. Tripathi S, Sahu U, Meshram J, Kumari R, Tripathi D.K, Ajazuddin, Alexander A, Sharma H, Sahu G. (2018). Research article Formulation and characterization of virgin coconut oil emulsion (vcoe) for treatment of alzheimer’s disease. Research Journal of Pharmaceutical Dosage Forms and Technology. Issue-02 April- June; 1-6.

58. Sharma H, Sahu G. K., Dapurkar V. (2012). Review article; An overview of new drug delivery system: Microemulsion; Int. Res J Pharm. App Sci.; 2(5): 1-8

59. Sahu G, Sharma H, Kaur C.D. (1960). Review article; Evolving concepts and targeting of arthritis; World Journal of Pharmaceutical Research, Vol 3,

60. Sahu G, Sharma H, Kaur C.D. (2013). Review article; A Novel Approach of Magnetic Modulated Microspheres; Asian J. Pharm. Res; Vol. 3: Issue 4, Pg 220-224

61. Sahu G, Sharma H, Dapurkar V, Rai G. (2012). Research article; Development and Evaluation of Methotraxate Loaded BSA Microspheres; Int. Res J Pharm. App Sci.; 2(5): 9-12

62. Sahu S K, Ajazuddin, Banjare T, Gupta S, Bhandarkar A, Sahu H, Diwedi S.D, Sahu P, Agrawal P, Yadav P, Bhatt A, Sahu K, Dewangan D, Thapa H, Deepika, Sahu G, Sharma M, Tripathi D.K., Alexander A. (2018). Research article; Formulation and evaluation of orodispersible tablet of montelukast sodium; Research J. Pharm. and Tech. 11(3)

63. Sharma H, Dapurkar V K, RaiG, Sahu G K. (2012). Research article; Microemulsions for the Topical Administration of 5- Fluorouracil: Preparation and Evaluation; Research J. Pharm. and Tech. 5(8).

64. Tripathi S, Sahu UM, Meshram J, Kumari R, Tripathi D.K., Ajazuddin, Alexander A, Sharma H, Sahu G. (2018). Reasearch article, Formulation and characterization of Virgin Coconut Oil Emulsion (VCOE) for treatment of Alzheimer’s disease; Research Journal of Pharmaceutical Dosage Forms and Technology. 10(2).

Received on 10.04.2019 Modified on 17.06.2019

Research J. Pharm. and Tech. 2019; 12(11):5437-5443.

DOI: 10.5958/0974-360X.2019.00943.0