Vol 12, Issue 1, 2019 Online - 2455-3891 Print - 0974-2441 FORMULATION DEVELOPMENT AND EVALUATION OF PRONIOSOMAL GEL OF ETHINYLESTRADIOL AND LEVONORGESTREL FOR ANTIFERTILITY TREATMENT SHIKHA BAGHEL CHAUHAN 1 *, TANVEER NAVED 2 , NAYYAR PARVEZ 3 1 Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India. 2 Department of Pharmaceutics, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India. 3 Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India. Email: shikha.pharma@gmail.com Received: 05 September 2018, Revised and Accepted: 22 November 2018 ABSTRACT Objective: The purpose of this research was to develop and formulate proniosomal gel drug delivery system of ethinylestradiol and levonorgestrel for antifertility treatment that is capable of efficiently delivering entrapped drug over an extended period of time. Methods: Ethinylestradiol and levonorgestrel are encapsulated in various formulations of proniosomal gel composed of various ratios of span surfactant, cholesterol, soya lecithin, and alcohol as aqueous phase prepared by coacervation-phase separation method. The prepared formulations characterized for drug encapsulation efficiency, size distribution, in vitro release studies, and vesicular stability at different storage conditions were carried. Stability studies for proniosomal gel were carried out for a few weeks. Morphological size and shape of the vesicles are characterized using optical microscopy and scanning electron microscopy (SEM). Stability studies for proniosomal gel were carried out for 3 months. Results: Morphological size and shape of the vesicles are characterized using optical microscopy and SEM, particles are found to be spherical, size of the particles is in the range of 46.4–80.6 nm, and permeation studies showed good control release for prolonged period of time. The encapsulation efficiency of proniosomal gel formulations is in the range of 74–80% and in vitro permeation studies proved that good amount of drug is permeated and has reasonably good stability characteristics as well. Conclusions: The results suggest that proniosomal gel formulations of ethinylestradiol and levonorgestrel may be used for transdermal delivery for antifertility treatment. The dried proniosomal formulation could act as a promising alternative to niosomes. Keywords: Estradiol, Formulation development, Levonorgestrel, Transdermal matrix patches. INTRODUCTION Contraception was used by women in the form of pills, intrauterine device, Norplant, foaming tablets, nasal spray, and condoms, and coitus interruptus was used by men. Limitation of contraceptive is mainly their side effect and failure rate related to the consumer compliance. Vesicular structures such as niosomes, ethosomes, transfersomes, and liposomes are favorable systems to go this permeation barrier. But their main disadvantage is their instability, which can be overcome by the usage of provesicular tactics like proniosomes, proliposomes and provesicular, protransfersomes procedures which can further enhance the efficacy of vesicles. These approaches may triumph over pores and skin barrier properties and beautify percutaneous absorption. In these systems, hydrophilic and lipophilic pill drugs may be integrated. The proniosomes are dry formulation which is water-soluble carrier, covered with surfactant, it is dehydrated to make niosomal dispersion and can be rehydrated by agitating in hot aqueous media within few minutes. The ensuing niosomes are uniform in size. Proniosomes are the latest development in novel drug delivery device. These are most advanced drug provider in a vesicular system which overcomes demerits of liposomes and niosomes [1,2]. Ethinylestradiol is regularly utilized in female hypogonadism, and treatment of prostate cancer, as the estrogenic component of combined oral contraceptive and it is frequently used in menopausal symptoms, as the estrogen for menstrual disorders and estrogenic component for combined oral contraceptive and with the daily dose of ethinylestradiol is 20–50 µg [3]. Levonorgestrel is a powerful progestogen and has been broadly prescribed as a contraceptive steroid for female fertility regulation. It has been found that, if progestin alone is used as a contraceptive, it produced episodes of irregular and unpredictable spotting and numerous untoward effects. Their side effects were the main reasons why women discontinued its use. The daily day dose of levonorgestrel is 30–37 µg in step with day. Alone use of progestin is less efficacious than combination oral contraceptives. Therefore, the study indicates that the combined mixture of ethinylestradiol and levonorgestrel turned into a powerful contraceptive formulation. Therefore, the objective of the study is to formulate the proniosomes of levonorgestrel and ethinyl estradiol for antifertility treatment [4]. MATERIALS AND METHODS Materials Levonorgestrel and ethinylestradiol were received as a gift sample from Cochin and Ontop Pharmaceuticals Ltd., Bengaluru. Cholesterol, soya lecithin, Span 20, and alcohol were procured from S. D. Fine Chemical Ltd., Mumbai, and Central Drug Store. All chemicals were used as received without any further purification. Method of preparation Proniosomal gel was prepared by a method known as coacervation- phase separation method. Precise amounts of non-ionic surfactant, cholesterol, lecithin, and drug (10 ml) were weighed and taken in a clean and dry wide-mouthed glass flask of 5.0 ml capacity, and alcohol was further added to it. All the ingredients such as cholesterol and lecithin were mixed well with a glass rod; the open end of the glass bottle was covered with a lid to prevent the loss of solvent from it and warmed over a water bath at 60–70°C for about 5 min until the surfactant mixture was dissolved completely. Then, the aqueous phase © 2019 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2019.v12i2.29546 Research Article