Modification of a Unani pharmacopoeial formulation Zimad-e-Jarbin to Lotion form and evaluation of Physicopharmaceutical parameters

Introduction

The application of medicinal substances to the skin and its appendages, such as sweat glands, nails, and the pilosebaceous unit, as well as to various body orifices, is an age-old practice. Ancient Egyptian papyrus records document numerous external medications, while Galen, in Roman times, described an early precursor to modern vanishing creams[1]. In spite of many dosage forms available in Unani System of Medicine to be used locally to treat different body ailments or skin diseases or as cosmetics, they didn’t use frequently and hence not getting acceptance among patients and physicians may be due to compromised physical characteristics. Therefore, they have fallen into disuse because of advances in the practice of medicine. The physical characteristics of these locally applicable dosage forms are not patient compatible. Bad odour, difficult in application, staining on cloths, consistency and packaging are the main issues. Therefore, to make them patient compatible with acceptable physical characteristics as per today’s requirement, it is necessary to redesign these traditional dosage forms in all aspect as per their indication and application [3-4]. The recent trend in traditional medicine dosage forms is to enhance the solubility, bioavailability, pharmacological activity, stability, attractive dosage forms, better patient and physician compliance, and toxicity reduction etc. [2]. Zimaad (Medicated paste/ Ointments/Liniments) or [Ḍimād – ضماد] is a traditional powder-based formulation that is mixed with specific oils, water, or other liquids at the time of use to form a paste for topical application. It is primarily used for two purposes: (i) alleviating pain in specific organs, such as headaches (Suda’a), arthritis (waja-ul-mafaasil), and chest pain (waja-us-sadr), and (ii) reducing swelling in organs like the liver (Kabid), spleen (Tihaal), and stomach (M’eda) [5].Lotions, on the other hand, are low- to medium-viscosity topical formulations designed for application to intact skin. They can be applied using bare hands, clean cloths, cotton wool, or gauze and provide a cooling effect due to solvent evaporation. Compared to solutions, lotions have a thicker, more emollient texture. [6] This delivery system offers several advantages, including bypassing first-pass metabolism, ease of application, enhanced patient compliance, improved physiological and pharmacological effects, minimized gastrointestinal incompatibility, and the ability to discontinue treatment when necessary.

Scabies is a neglected tropical skin disease caused by the infestation of the mite Sarcoptesscabiei var. hominis. The female mite, measuring less than 0.5 mm, burrows into the skin, triggering a hypersensitivity reaction due to antigens present on its exoskeleton, as well as its saliva, excreta, and eggs [7-8]. This immune response leads to intense itching and the development of stigmatizing skin lesions.While conventional medicine offers various therapeutic options, many treatments are associated with adverse effects such as nausea, vomiting, weakness, tremors, irritability, disorientation, and neurotoxicity, particularly in formulations containing gamma benzene hexachloride 1%. In Unani medicine, topical applications are traditionally preferred for treating Jarb (scabies). Classical Unani texts mention several Tila (medicated oils) and Zimad (pastes) for this condition. Zimad-e-Jarb, a pharmacopoeial formulation described in Byaz-e-Kabir,possesses Muhallil (resolvent), Jali (detergent), Dafa-e-Ta’ffun (disinfectant), and Mundammil-e-Qurooh (cicatrizant) properties. It has been extensively used in Unani medicine for managing scabies, offering a natural and holistic approach to treatment.

Thus, in this study Zimad-e-Jarb a Unani Pharmacopoeial preparation mentioned in Biyaz-e-Kabeerwas selected for redesign to Lotion form and also standardized on some physical and pharmaceutical parameters.

Materials and Methods

Procurement of Drug Material

The drugs namely Copper Sulphate (Neelathotha), Sulphur (Gandhak), Lead oxide (Murdarsang) and MallotusphilippinensisMuell (Kameela) were obtained from DawakhanaTibbiya College, Aligarh Muslim University, Aligarh. All the drugs except Kameela were authenticated and identified on the basis of chemical tests performed on the given sample of drugs by Dr. Mohammad Zain Khan, Assistant Professor, Department of Industrial Chemistry, A.M.U., Aligarh. Kameela was authenticated and identified by Dr. Sumbul Rehman, Assistant Professor, at the Pharmacognosy section, Department of IlmulAdvia, Faculty of Unani Medicine, A.M.U., Aligarh.

Preparation of Lotion from Zimad-e-Jarb

The drug ingredients were grinded and made powder separately and then wet grinded with Araq-‎e-Gulab in an electric mortar and pestle for 6hrs at 20rpm respectively. The powder ‎not let to dry during the grinding and Araq-e-Gulab was added time to time when ‎needed. Now the wet grinded powder placed in the oven at 80-95˚C for the removal ‎of moisture. After complete drying, powder was sifted through sieve no 100 to obtain ‎very fine powder. Thereafter, take finely grinded 3gm powder of each ingredient and ‎put in a 100 ml beaker individually. Added 30 ml of alcohol to the Kamela powder as it is ‎insoluble to water and oil, NeelaThotha was dissolved in 57ml of distilled water and ‎‎7ml of glycerol was used to dissolve Gandhak and Murdarsang (soluble in glycerol ‎and not in water). After proper mixing of each ingredient to their respective solvents, ‎they mix together in a large beaker.  To get homogenous mixture of aqueous phase the ‎solution was put on heating plate equipped magnetic stirrer at 70˚C for 1 hour. Add ‎Triethylamine 12ml, Methylparaben 0.1%, Propylparaben 0.02%, Polysorbate 80. 3ml ‎into the above solution slowly and one by one.‎

To make oil phase required quantities of Almond oil, Acetyl Alcohol, and Stearic ‎Acid, were taken as mentioned in table 2 and mix together by putting on heating plate ‎equipped magnetic stirrer at 60˚C for minimum 20 minutes.‎

Now add aqueous phase into oil phase slowly with continuous stirring with the help of ‎the magnetic stirrer and left for stirring at least for 40min at 50rpm. After homogenous ‎mixing the solution left to cool for 1hour. Lastly add and mix menthol 0.1% and ‎titanium dioxide 1gm into the solution to get color and odor of the prepared ‎Lotion [12][13][14]‎. TheingredientofZimad e Jarbaregivenintable 1.

Physico-pharmaceutical Evaluation of formulated Lotion

Organoleptic Characteristics

Organoleptic characterization like colour, odour, appearance and texture was done by physical examination and documented [12][13].

Foreign Particles
A thin layer of the formulation was evenly spread on a glass slide and examined under diffused light to detect the presence of any foreign particles or impurities.

Homogeneity
The homogeneity of the formulation was assessed through visual inspection and tactile evaluation to identify any inconsistencies in texture, such as clogs or uneven distribution.

pH

The pH of 1% and 10% solution of the lotion was measured by using digital pH meter [12][14].

For preparation of a 1% solution of a lotion, take a 100ml graduated cylinder, fill it with distilled water upto 99ml mark. Now pour 1ml of lotion into it. And for making 10% solution add 10 ml of lotion to 90ml distilled water in a graduated cylinder. Calibrate the pH meter and measure the pH at room temperature.

Viscosity:

Viscosity was determined by Brookfield Digital Viscometer by using spindle no. L-2, at room temperature and rotation per minute was 30 [13].

Spreadability of a lotion

Two glass slides (20 × 5 cm) were selected for the experiment. The formulation was applied evenly onto one slide, and the second slide was placed on top, ensuring the formulation was uniformly sandwiched between them. A 100 g weight was placed over the slides to create a consistent thin layer. After removing the weight, any excess formulation adhering to the slides was carefully scraped off.

The slides were then positioned in a fixed stand, with the lower slide securely held by the opposite fangs of the clamps while allowing the upper slide to move freely. A 60 g weight was carefully attached to the upper slide. The time (in seconds) required for the upper slide to travel a distance of 5 cm and completely separate from the lower slide under the applied weight was recorded[12].

Washability Test

A measured portion of the lotion was applied to the skin on the hand and exposed to a continuous flow of tap water for 10 minutes. The time taken for the lotion to be completely washed off was carefully observed and recorded[15][16].

Irritancy Test/Patch Test/Sensitivity Test:

Sensitization of skin is measured with patch test. As various types of ingredients are used thus, there may be a possibility of sensitization of the skin. The test sample (lotion) was applied on the dorsal left hand surface of 05 individuals. Irritancy, erythema, edema was checked every hourupto 24 hours and reported[12].

Observations and Results

The results of  redesigned  Zimad-e-Jarb, a Unani pharmacopeial preparation to a Lotion form are depicted as follows.

Physico-pharmaceutical evaluation of Lotion form of Zimad-e-Jarb

Organoleptic Characteristics: The redesigned formulation of Zimad-e-Jarb i.e. lotion appeared as liquid, smooth in texture having an aromatic odour and olive green in colour .

Foreign particles: Lotion was observed against the diffused light on the glass slide showed no foreign particles in the lotions.

Homogeneity: The results showed that the lotion was a homogeneous mixture having no clogs.

pH: The pH of 1% and 10% solution of the lotion was measured by using a digital pH meter and found to be 5.23±0.03and 5.14±0.01respectively as shown in table 2.

Viscosity: Viscosity was determined by Brookfield Digital Viscometer and found as 368.4±1.8cps (Table 2)

Spreadibility of Lotion

The spreadability of the lotion was determined and found as 7.94±0.20 g.cm/s as depicted in table 2.

Washability Test

A small amount of lotion was applied to the dorsal aspect of the hand and rinsed under tap water. The formulation was observed to be easily washable, ensuring convenient removal upon application.

Irritancy Test

There was no irritancy, erythema, or edema observed after 24 hours of the application of lotion on the dorsal surface of the left hand. Thus, the lotion was found to be safe and well-tolerated.

Discussion

There are many medications or dosage forms in Unani system of medicine which can be applied on skin to treat different diseases. In any system of medicine, drug designing and redesigning are the major concerns as it is not just the efficacy and potency that have an important role, but physical features like appearance, shape, taste, colour etc. also plays a significant role in the use of medicines. Thus, it is necessary to modify Unani dosage forms eventually which help in global recognition of Unani System of Medicine.Zimad is the powder of many or single drugs, converted in to paste before application by mixing in any of the specified oils, water etc‎. It mainly used for treating pain and inflammation alongwithedema of any organ having anti-inflammatory, antiseptic, haemostatic and astringent properties‎[10][17].Difficulty in application, staining on cloths, irregular consistency, odour and packaging are the main issues. Therefore, to make them patient compatible with acceptable physical characteristics as per today’s requirement, it is necessary to redesign it into lotion form. They are thicker and emollient in nature in comparison to solution. After preparation of a new dosage form it is very much basic to standardize the new formulation on physico-chemical and pharmaceutical parameters for quality assurance and generate specifications for future.Organoleptic evaluation is most straight forward and quickest way to analyze the formulations[18]. The lotion was analysed for, color, texture, odor and appearance and found as olive green, smooth, aromatic liquid.  Homogeneity is a crucial parameter in an emulsion, as a smoother and more uniform texture indicates a well-formulated lotion. It reflects the proper mixing of the oil and water phases, the lotion exhibited a high level of homogeneity, with no visible phase separation between the oil and water components. Additionally, no clogs or inconsistencies were observed in the emulsion, confirming its stability and uniformity.The pH is also an important parameter for quality and can be adjusted to improve the stability of the formulations or make it suitable to use at the site of application. It also affects drug permeation through the skin [20]. The pH of a topical formulation should be close to that of human skin to prevent irritation, dryness, or discomfort. Maintaining an appropriate pH ensures the product is gentle, well-tolerated, and safe for regular use on the skin[21][22]. The pH of 1% and 10% solution of the lotion was found to be 5.23±0.03and 5.14±0.01 respectively and within the range of normal skin pH i.e. 4.0 to 7.0.Viscosity is an important physical property of topical formulations that may affect the rate of drug release and influences skin application (spreadability and skin feel). When the viscosity is too low, spread very fast as it quickly runs off after applying to the skin [21][22]. The viscosity of the lotion was measured using a Brookfield Digital Viscometer and recorded as 368.4±1.8 cps. Spreadability is a crucial parameter that determines the ease of application and distribution of the active ingredients in the lotion. A good lotion should spread easily with minimal effort, enhancing user convenience. The spreadability value of 7.94±0.20 g.cm/s indicates that the lotion required minimal shear force for application, making it easy to use while maintaining acceptable bioadhesion. The washability test was conducted to assess the ease of removal from the skin. The lotion was found to be easily washable, leaving no residue or stains after rinsing, ensuring user comfort and convenience.To know thesafety of lotion, Irritancy Test was done on 05 individuals. There was no sign of inflammation, lesion or irritation was developed during the test duration. Thus, the lotion, a redesigned dosage form of Zimad-e-Jarb was safe and well tolerated to use locally.

CONCLUSION

The medicated “Lotion” dosage form is the right candidate for substitution of at least a fraction of Unani traditional dosage form “Zimad-e-Jarb”. The studies suggest that the “Lotion” dosage form of “Zimad-e-Jarb” is much more convenient, compatible, and has better compliance of the patient, than “Zimad-e-Jarb” itself. The tests results of Physico-pharmaceutical analysis of the Lotion form of Zimad-e-Jarb, shall be considered as standard quality control parameters to avoid batch to batch variation and can be used for future references. The formulation further studied for systemic absorption to analyze any systemic effect or toxicity produce due to redesigned form of lotion.

REFERENCES

1. Felton, L.A.Remington-essentials of pharmaceutics. Pharmaceutical press. 2013.
2. Zaigham, H., Tauheed, A. and Ali, A.Recent trend in traditional medicine dosage form and present status of Unani and Ayurvedic medicine. Int J Pharm Sci & Res. 2019. 10(4), pp.1640-49.
3. Anonymous, 2012. Standard Unani Medical Terminology, Central Council for Research In Unani Medicine, Department of Ayurveda, Yoga, & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH),Ministry of Health & Family Welfare, Government of India, 61-65, Institutional Area, Opposite ‘D’ Block, Janakpuri, New Delhi – 110 058 (India). p. 129.
4. Anonymous. National Formulary of Unani Medicine Part-IV (revised), Govt. of India, Ministry of AYUSH, New Delhi. 2020. p 4,218.
5. Garg, T., Rath, G. and Goyal, A.K.Comprehensive review on additives of topical dosage ‎forms for drug delivery. Drug delivery.2015. 22(8), pp.969-987.‎
6. Meyer J., Marshall B., Gacula Jr M., Rheins L. Evaluation of additive effects of ‎hydrolyzed jojoba (Simmondsia chinensis) esters and glycerol: a preliminary study. J ‎Cosmet Dermatol. 2008. 7, 268–74.‎
7. Hay, R.J., Steer, A.C., Engelman, D., Walton, S. Scabies in the developing world-Its ‎prevalence, complications, and management. Clin. Microbiol. Infect. 2012. 18, 313–323.
8. Engelman, D. and Steer, A.C.Control strategies for scabies. Tropical medicine ‎and infectious disease, 2018.3(3), p.98.‎
9. Anonymous.  The Unani Pharmacopoeia of India Part I Vol I, Department of Ayurveda, Yoga, & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH),Ministry of Health & Family Welfare, Government of India, 61-65, Institutional Area, Opposite ‘D’ Block, Janakpuri, New Delhi – 110 058 (India) . 2007. p44.
10. Anonymous. National Formulary of Unani Medicine, Part VI, Central Council for Research In Unani Medicine, Department of Ayurveda, Yoga, & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH),Ministry of Health & Family Welfare, Government of India, 61-65, Institutional Area, Opposite ‘D’ Block, Janakpuri, New Delhi – 110 058 (India). 2011. p187, 154-155.
11. Kabiruddin H.M. Biyaz Kabeer. Part 2 New Delhi: IdaraKitabul Shifa.2014.p125.
12. Rathi, N.M., Sirsat, S.V., Tayade, S.S., Khot, A.S. and Deshmukh, A.C.Formulation and Standardization of Herbal Lotion: A Review.  International Journal of Novel Research and Development .2022. 7(4), pp.604-610.
13. Saptarini, N.M. and Hadisoebroto, G.Formulation and evaluation of lotion and cream of ‎nanosized chitosan-mangosteen (Garcinia mangostana L.) pericarp extract. Rasayan J ‎Chem. 2020. 13(2), pp.789-95.‎
14. Verma H. and Sisodiya D. Formulation and Evaluation of Herbal Lotion of Aloe Vera (Aloe Barbadensis) Sch Acad J Biosci. 2020.8(1): 7-10‎.
15. Gyawali, R., Paudel, N., Shrestha, S. and Silwal, A.Formulation and evaluation of antibacterial and antioxidant polyherbal lotion. Journal of Institute of Science and Technology.2016.21(1), pp.148-156.
16. Pandit, S.S.,Hingane L.D. 2022.  Preparation and Evalution of Herbal Body Lotion.
17. Anonymous. National Formulary of Unani Medicine, Part I (revised), Govt. of India, Ministry of AYUSH, New Delhi. 2019.p220
18. Ahmed S, Hasan MM., 2015. Standardization of crude drugs: a precise review. World Journal of Pharmaceutical Research.2015. 4(10):155-74.
19. Fransiska, D., Darmawan, M., Sinurat, E., Sedayu, B.B., Wardhana, Y.W., Herdiana, Y. and Setiana, G.P.Characteristics of Oil in Water (o/w) Type Lotions Incorporated with Kappa/Iota Carrageenan. In IOP Conference Series: Earth and Environmental Science .2021. Vol. 715, No. 1, p. 012050). IOP Publishing.
20. Woodall R, Arnold JJ, McKay D, Asbill CS.Effect of formulation pH on transdermal penetration of antiemetics formulated in poloxamer lecithin organogel.Int J Pharm Compd.2013. 17.
21. Milanowski B, Wosicka-Frąckowiak H, Główka E, Sosnowska M, Woźny S, Stachowiak F, Suchenek A, Wilkowski D. Optimization and evaluation of the in vitro permeation parameters of topical products with non-steroidal anti-inflammatory drugs through Strat-M® membrane. Pharmaceutics.2021. 13(8):1305.
22. Navindgikar, N., Kamalapurkar, K.A. and Chavan, P.S.Formulation and evaluation of multipurpose herbal cream. International Journal of Current Pharmaceutical Research.2020.12(3), pp.25-30.
23. Chaudhary, H., Rohilla, A., Rathee, P. and Kumar, V.Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers. International journal of biological macromolecules. 2013. 55, pp.246-253.