FORMULATION AND EVALUATION OF OCUSERTS OF CIPROFLOXACIN HCl

Conventional ocular drug delivery system i.e., eye drops, ointments, gels etc., had become less popular pertaining to their disadvantages like evaporation by tears, pre-corneal loss, drug metabolism, drug-protein interaction, drainage, sticking of eye lids, induced lacrimation, poor patient compliance, systemic side effect and blurred vision etc. That’s why fundamentals of controlled release by means of ocular inserts were utilized to increase problem pre-corneal drug residence time.
This project title “Formulation and Evaluation of Ocuserts of Ciprofloxacin HCl” revealed following results:
 Compatibility study using FTIR was performed to check the compatibility of drug with various excipient. Characteristics peaks obtained with pure drug were compared with that produced with different excipients that confirmed the compatibility of drug with excipients.
 Ocusert of Ciprofloxacin HCl was prepared using different material i.e., PVP K-30, PVA, PEG 400 and glycerin.
 Prepared ocuserts were evaluated for various parameters viz., percentage moisture loss, percentage moisture absorbs, thickness, weight variation, drug content and In-vitro diffusion.
 The percentage (%) moisture absorption and loss of ocular insert were found to be 26% and 27% respectively.
 The thickness of ocular insert was found to be uniformed and its mean while measuring at different points was found to be 0.124mm.
 The weight of ocular inserts was found to be in the range of 12.2 - 12.6mg which indicated decent distribution of the drug, polymer and plasticizer.
 The drug content of ocular insert was found to be 99.89%.
 Percentage drug release from Ciprofloxacin HCl Ocusert was found to be 41.969% in 8 hr.
It was concluded that prepared Ocusert of Ciprofloxacin HCl could be a better alternative to conventional ocular formulations that retained on ocular surface for longer duration and released drug in controlled manner.

1. A PRESENTATION ON FORMULATION AND EVALUATION OF OCUSERTS OF CIPROFLOXACIN HCl Submitted for the partial fulfilment of the award of the degree of Bachelor of Pharmacy By MOHAMMAD ADIL Enrollment No. TPH1102033   Approved by Supervised by PROF. (DR.) K. K. JHA MRS. SHAWETA SHARMA (Director) (Asst. Prof.) TEERTHAKER MAHAVEER COLLEGE OF PHARMACY TEERTHANKER MAHAVEER UNIVERSITY MORADABAD 2015- 2016 1

2. INTRODUCTION Eye is an essential organ with unique qualities and enable us to see the world. Eye sicknesses can influence the body and consequently led to loss of vision also. Therefore, many traditional and new ocular drug delivery systems are available. Most commonly available ophthalmic preparations i.e. eye drops and ointments covers about 70% of the total formulations in market. From conventional dosage forms, just a little amount is available for its therapeutic effect resulting in frequent dosing. That’s why to overthrown these issues, newer pharmaceutical formulation such as In-situ gel, nanoparticles, liposomes, nanosuspension, microemulsion, iontophoresis and ocular inserts have been developed to increase the bioavailability of the drug in sustained and controlled manner. 2

3. CLASSIFICATION OF OCULAR DRUG DELIVERY SYSTEMS: - Ocular drug delivery system are classified as: Liquids : - Sprays, sol-gel systems, suspensions & solutions. Solids : - Ocular inserts, artificial tear inserts, contact lenses, filter paper strips & corneal shield. Semi-solids : Gels & ointments. Miscellaneous : Ocular iontophoresis, Muco-adhesive dosage forms & vesicular systems. 3

4. OCUSERTS: Ocular inserts have been developed through which the drug is delivered at a near constant known rate based on diffusional mechanisms. Minimizes side effects by avoiding excessive absorption peaks. The delivery of pilocarpine by such an insert was commercialized in 1975 (ocuserts Pilo) by Alza corporation. The ocuserts was designed to be placed in the lower cul-de-sac to provide a weekly dose of pilocarpine and removed & replaced by a new one after completion of time. The near zero-order rate delivery is based on the selection of an non-eroding copolymer membrane enclosing the drug reservoir. Placement of ocusert into eye 4

5. ADVANTAGES OF OCUSERTS: Increased contact time that led to enhanced bioavailability. Possibility of providing a prolonged drug release and in consequence a better efficacy. Administration of a precise dose in the eye and thus an improved therapy. Decrease of systemic side effects and adverse effects. Reduction of the number of administrations and thus improved patient compliance & ease. Lack of explosion. Ease of handling and insertion. Reproducibility of release kinetics. Sterility. Better stability. Exclusion of additives. Improved shelf life with comparison to aqueous solutions due to lack of water . 5

6. MECHANISM OF DRUG RELEASE Drug release from Ocusert involves one of following mechanisms: Diffusion Osmosis Bio-erosion 6

7. METHODS OF PREPARATION OF OCUSERTS Solvent casting method Glass substrate technique Melt extrusion technique 7

8. S.No . AUTHOR NAME TITLE & JOURNAL FINDINGS 1. Sneha prabha Lad et al. (2016) “Design of ocular controlled release ocuserts of brinzolamide ”, Int J Pharm 2016; 6(2): 191-202 In-vitro diffusion and In-vivo studies revleaed 82.0% ± 0.594 & 80.00 ± 1.003% respectively. Drug polymer compatibility was confirmed by IR & DSC studies. 2. Sayani Bhattacharyya et al. (2015) “Preparation and Evaluation of Ophthalmic Inserts of brimonidine tartrate”, IJPCBS 2015, 5(1), 177-183 It was found that Inserts containing HEMA plasticized with DBP indicated better shape holding properties and a controlled drug release. 3. Narendra V et al . (2014) “Azithromycin β –cyclodextrin ocular films: Preparation and Evaluation”, IJCPS, 2014, Vol.2(11): 1265-1269 The prepared ocular films gave satisfactory physicochemical characteristics and in-vitro release characteristics 4. Vivek Dave et al . (2013) “Formulation and evaluation of controlled delivery of Aceclofenac through ocular insert”, Turk J Pharm Sci., 2013, 10 (2), 205-220 It was observed that 98.24% drug was released from the formulation consisted of 3% HPMC while it was 70.25% with 3% Ethyl Cellulose for a period of 24 hr and followed zero order kinetics. 8 REVIEW OF LITRATURE

9. 5. Kaul Shweta et al . (2012) Development and In-vitro characterization of ocular insert containing erythromycin, IRJP 2012, 3 (8) Pg. no. 246-250 It was concluded that the Erythromycin ocuserts would be able to offer benefits such as increased residence time, prolonged drug release, reduced frequency of administration, and thereby might help to improve patient compliance. 6. T.K. Ghelani et al . (2011) Formulation and Evaluation of Timolol Maleate Ocular Insert, Asian Journal of Biochemical and Pharmaceutical Research 2011, (1), 167-174 In-vitro release study was carried out for all formulations and overall results revealed that as concentration of polymer increased, the drug release was decreased. 7. A. Rajasekaran et al . (2010) Design and evaluation of polymeric controlled release Natamycin ocular inserts, Kathmandu university journal of science, engineering and technology 2010, 6 (I),108-115 FTIR studies indicated no possibility of interaction between drug and polymer and all formulations showed no change in physical appearance. The formulation consisted of 3% Eudragit RL 100 and 1% Eudragit L 100 showed expected zero order release for one day. 9

10. 8. Hitesh B. Gevariya et al . (2009) Sustained ophthalmic delivery of levofloxacin from once a day ocuserts, International Journal of Pharmacy and Pharmaceutical Sciences, 1 (1), Nov.-Dec. 2009 pg. no. 24-32 In-vitro drug release studies revealed that, the formulation with PEO/EC (3:7) was found to be better than the other formulations . The formulation L6 followed perfect zero order kinetics release (n=1.03) while rest of formulations released super case II kinetics (n>1). 9. Shreenivas et al. (2006) Ofloxacin ocular inserts: Design, Formulation and Evaluation, IJPT 5:159-162, 2006 Best formulation showed maximum cumulative percentage drug release of 91.27 % at the end of 24 hr. Prepared ocuserts were also passed the test for sterility & showed zero-order drug release in the in-vitro and in-vivo release studies. 10. Venkateshwar RAO et al. Preparation and Evaluation of Ocular Inserts Containing Norfloxacin, Turk J Med Sci 34 (2004) 239-246 All the prepared films were found to be uniform in thickness and the partition coefficient of norfloxacin and its beta cyclodextrin complex was 0.048 and 0.853 respectively. I.R. spectra revealed complexation of norfloxacin with b-cyclodextrin. 10

11. ADOPTED METHODOLOGY PREPARATION OF STANDARD CALIBRATION CURVE DRUG EXCIPIENT COMPATIBILITY STUDIES BY USING FTIR 11

12. PREPARATION OF OCUSERTS S.No. Ingredient Amount 1. Ciprofloxacin HCL 100 mg 2. Poly Vinyl Pyrrolidone (K-30) 500 mg 3. Poly Vinyl Alcohol 500 mg 4. Poly Ethylene Glycol 400 0.5 ml 5. Glycerine 25 mg Ocusert of ciprofloxacin was prepared with three different polymers by solvent casting method. 12

13. EVALUATION OF OCUSERTS OF CIPROFOLAXCIN: Percentage (%) moisture absorption Percentage (%) moisture loss Uniformity of thickness Uniformity of weight Drug content In vitro drug release studies 13

14. EXPERIMENTAL STUDIES: Spectrophotometric scan of Ciprofloxacin HCl: The λ max of ciprofloxacin hcl was found to be 278nm. U.V scan of Ciprofloxacin HCl in 0.1N HCl 14 RESULT AND DISCUSSION

15. Validation of λ max Overlain spectra of ciprofloxacin HCl 15

16. Preparation of standard curve of ciprofloxacin HCl: S. No. Concentration ( µg/ml) Absorbance 1. 2 0.195 2. 4 0.389 3. 6 0.598 4. 8 0.795 5. 10 0.989 Concentration v/s absorbance data of Ciprofloxacin HCl in 0.1N HCl Calibration curve of Ciprofloxacin HCl in 0.1N HCl 16

17. DRUG - EXCIPIENT COMPATIBILITY STUDY BY FTIR FTIR scan of Ciprofloxacin HCl (pure drug) FTIR scan of formulation blend 17

18. EVALUATION OF OCUSERTS: Percentage (%) moisture absorption: The percentage (%) moisture absorption of ocusert was observed to be 26%. Percentage (%) moisture loss: The percentage (%) moisture loss of ocusert was observed to be 27% Uniformity of thickness: The mean thickness of ocusert measured at different points was found to be 0.124mm. Uniformity of weight: The weight of ocusert was observed to be in the range of 12.2 - 12.6mg. It showed great distribution of the drug, polymer and plasticizer. Drug content: The drug content of ocular insert was found to be 99.89%. 18

19. In vitro drug release study of Ocusert of Ciprofloxacin HCl: Sr. No. Time (hrs.) Absorbance Concentration (µg/ml) Amt. in 30ml % Drug Release   1 0.191 1.923 0.577 8.127   2 0.212 2.135 0.640 9.021   3 0.363 3.655 1.097 15.447   4 0.620 6.244 1.873 26.382   5 0.732 7.372 2.212 31.148   6 0.803 8.087 2.425 34.169   7 0.898 9.043 2.713 38.211   8 0.988 9.949 2.984 41.969 Percentage drug release from Ciprofloxacin HCl Ocusert 19

20. CONCLUSION This project title “Formulation and Evaluation of ocuserts of ciprofloxacin HCl” revealed following results: Compatibility study using FTIR was performed to check the compatibility of drug with various excipient. Characteristics peaks obtained with pure drug were compared with that produced with different excipients that confirmed the compatibility of drug with excipients. Ocusert of ciprofloxacin HCl was prepared using different material i.e., PVP K-30, PVA, PEG 400 and glycerin . Prepared ocuserts were evaluated for various parameters viz., Percentage moisture loss, percentage moisture absorbs, thickness, weight variation, drug content and in-vitro diffusion. The percentage (%) moisture absorption and loss of ocular insert were found to be 26% and 27% respectively. The thickness of ocular insert was found to be uniformed and its mean while measuring at different points was found to be 0.124mm. The weight of ocular inserts was found to be in the range of 12.2 - 12.6mg which indicated decent distribution of the drug, polymer and plasticizer. The drug content of ocular insert was found to be 99.89%. Percentage drug release from ciprofloxacin HCl ocusert was found to be 41.969% in 8 hr. It was concluded that prepared ocusert of ciprofloxacin HCl could be a better alternative to conventional ocular formulations that retained on ocular surface for longer duration and released drug in controlled manner. 20

21. REFERENCES Jitendra , sharma P.K, banik A., Dixit S. A new trend: ocular drug delivery system. International journal of pharmaceutical sciences 2011; 2(3):1-2. Http://anatomy.Iupvi.Edu www.Aioeyesurgeons.Com www.Myeyeworld.Com Patel hitesh A, patel jayavadan K., Patel kalpesh N, patel ravi R. Ophthalmic drug delivery system-a review. Scholars research library 2010; 2(4): 103. Williams Lippincott and Wilkens, Remington - the science and practice of pharmacy, 21 st edition, 2005, published by wolters kluwer company, page no. 850, 851 & 857 Yie.W . Chien , novel drug delivery systems 2nd edition,1982,100-120. Kaul shweta , kumar g., Kothiyal P. An insight into ocular insert. International journal of pharmaceutical sciences and research 2012; 3(7):1907-1908. Tangri p, khurana s. Basics of ocular drug delivery systems. International journal of research in pharmaceutical and biomedical sciences 2011; 2(4): 1547. Heller j. Controlled release of biologically active compounds from bio erodible polymers. Biomaterials 1980; 1:51-7. 21

22. THANK YOU 22