ANNEXURE-II

6. / Brief resume of the intended work:
6.1 Need for the study:
Skin is virtually the sole human surface directly interfacing the body with the external environment and it is the largest organ of the body receiving about 1/3rd of total blood circulating through the body. Though skin acts as an effective barrier for many agents, topically contacted xenobiotics can evoke both local and systemic effect. Skin is easily damaged either mechanically, chemically or biologically, thus micro-organisms can deliver contact allergens (1, 2).
Creams are semisolid systems with opaque appearance containing one or more medicinal agents dissolved or dispersed in O/W or W/O emulsion. After application of creams, the water evaporates leaving behind a thin residue film of oleaginous components or base. Creams are preferred over ointments as they are easier to spread and remove (3, 4).Creams are developed for wide application of anti-fungal and anti-microbial agents to treat dermal infections.
Sertaconazole nitrate is a drug of imidazole class. On oral administration, over 99% of sertaconazole is bound to plasma, but has poor bioavailability. Clinically, sertaconazole is used to treat skin infection such as athlete’s foot and seborrheic dermatitis. However, there are not many literatures available reporting in detail study of the development of sertaconazole cream. The above reasons necessitate the development of sertaconazole cream (5).
Like other imidazoleantifungals, sertaconazole inhibit the fungal cytochrome P45O ‘lanosterol 14-demethylase’ enzyme and thus impair ergosterol synthesis. Ergosterol is a critical component of the fungal cell membrane. Inhibition of ergosterol synthesis prevents fungal cell from multiplying and impairs hypae growth. Side effects are rarely seen with sertaconazole therapy, may include burning on application site and skin dryness (6, 7).
6.2 Review of Literature:
Borelli et al., (8)reported that sertaconazole nitrate is a broad spectrum anti-fungal agent for treatment of tineapendis and investigated the safety and efficacy of 2 % sertoconazole nitrate cream. After 4 weeks of treatment, 88.8% of participants achieved success with eradication of pathogen, 63.7% were free of erythma and 91.2% were free of itching. Based on these findings authors concluded that the drug is highly safe and effective in the treatment of tineapendisinterdigitalis.
Boni et al., (9) demonstrated safety and efficacy of 2% sertoconazole nitrate cream. Clinical studies in volunteers in the age group of 22-85 years (average age 56 years) indicated a significant improvement in the seborrheic dermatitis condition Thus they concluded that sertaconazole nitrate cream can be used for treatment of seborrheic dermatitis.
Shivanand et al. (10) formulated ketoconazole cream by preparing solid dispersion of the drug and then incorporating it into cream base by triturating. In vitro evaluation was carried out on the cream. Formulation containing more amount of mannitol gave maximum release of drug. The results thus obtained for assay and drug release were within limits.
Rajlaxmi et al., (11)formulated clotrimazole and ichthammol ointment to provide anti-fungal and anti-septic action. Formulation containing hard paraffin has low viscosity thus good spreadability and even diffusion is better. Thus they concluded that formulation containing hard paraffin gave better results compared to the formulation having white soft paraffin.
6.3 Objective of the study:
The objectives of the proposed study would be:
  • Preformulation study of the drug and selected excipients
  • Development of sertaconazole nitrate cream for topical application
  • Evaluation of the developed cream formulation
  • Stability studies of selected formulation as per ICH guidelines

7. / Material and Methods:
7.1 Source of data:
Preliminary data required for the experimental study would be obtained from scientific journals and scientific books.
7.2 Method of Collection of data:
Data on drug and excipients will be collected from the drug information center, standard books, catalogs, etc. On the basis of extensive preformulation trials on the drug and excipients, the final formulation will be developed.
i. Materials:
In the proposed work, the drug sertaconazole nitrate BP, with emulsifying agents like myristyl alcohol, polysorbate 60, light liquid paraffin and any other excipients will be used. Based on the preformulation studies, the excipients will be selected for development of formulation but ideally it contains stearyl alcohol as stiffening agent, octyldodecanol as thickening agent, cetyl alcohol as water absorbent, glycerylmonostearate as solubalizing agent and benzyl alcohol as preservative.
ii. Methods:
The cream with sertaconazole will be prepared by emulsification method. In first step the oil phase is prepared by melting at suitable temperature (70-75 C) stearylaclcohol or other wax materials. In second step, aqueous phase is prepared by mixing sertaconazole nitrate with sufficint quantity of water in a suitable vessel. The mixture is passed through colloidal mill to get a homogenous mixture. Final step of the preparation involves transferring of molten oil phase into aqueous phase. The temperature of the vessel and the contents is maintained well above the melting point of the ingredients of the formulation. The complete mixture is homogenized for 15mins. After complete homogenization, the mixture is cooled to room temperature.
iii. Evaluation
The prepared cream will be evaluated for homogeneity, viscosity, pH, drug content, preservative content, weight loss after stability, absence of specified micro-organism. Further, the prepared formulations will be evaluated for drug release by using diffusion cells as per the specified methods.
7.3 Does this study require any investigation or intervention to be conducted on patients or other animals? If so, please describe briefly.
No
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
Not applicable.
8. / References:
  1. Brahmankar DM, Jaiswal SB. Biopharmaceutics and Pharmacokinetics. New Delhi: Vallabh Prakashan.1995. 66.
  2. Lachman L, Lieberman HA. The Theory and Practice of Industrial Pharmacy. New Delhi: CBS publishers & Distributors. 2009. 534.
  3. Guru B, Sunil P. Semisolid Preparation. In: James Swarbrich, James C Boylan, editor. Encyclopedia of Pharmaceutical Technology. 2nded. New York: Marcel Dekker. 2002. Vol. 3, 24436.
  4. Allen LV, Popwich NG, Ansel HC. Pharmaceutical Dosage Forms and Drug Delivary System. 8thed. New York: LippimottWillians & Wilkins. 2005. 282.
  5. Croxtall JD, Plosker GL. Sertaconazole review of its use in the management of superficial mycoses in dermatology and gynaecology, Drugs 2009; 69:339-59.
  6. Eugene DW. Antifungal Agents. In: William O Foye, Thomas Lemke, David Williams, editor. Principles of Medicinal Chemistry. 4thed. New Delhi: Waverly publication.1974. 809.
  7. Tripati KD. Essentials of Medical Pharmacology. 6thed. New Delhi: Jaypee Brothers Medical; 2006. 761.
  8. Borelli C, Korting HC, Bödeker RH, Neumeister C. Safety and efficacy of sertaconazole nitrate cream 2% in the treatment of tineapedisinterdigitalis: A subgroup analysis. Cutis 2010; 85:107-111.
  9. Boni EE, Cantrell WC. An Open-Label Study of the Safety and efficacy of sertaconazole nitrate in the treatment of seborrheic dermatitis. J Drugs Dermatol 2011;10:895-9.
  10. Shivanand P, Devmurai V, Manish G, Pandey D. Formulation and optimization and in-vitro evaluation of Ketoconazole creams. Scholar Res Lib 2009; 1:18-24.
  11. Rajlaxmi G, Damodharan N, Janardhanreddy N, Vaghaji CVK. Formulation and evaluation of clotrimazole and ichthamol ointment. Int J Pharm Bioscience 2010;1: 7-13.

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