Cyclizine-Loaded Polymer Films Evaluation PDF

Cyclizine-Loaded Polymer Films: Evaluation, Characterization, and Anti-Emetic Effectiveness A Synopsis submitted to the Institute of Pharmacy, Bundelkhand University, Jhansi for the partial fulfilment of the degree of Master of Pharmacy...

Cyclizine-Loaded Polymer Films: Evaluation, Characterization, and Anti-Emetic Effectiveness A Synopsis submitted to the Institute of Pharmacy, Bundelkhand University, Jhansi for the partial fulfilment of the degree of Master of Pharmacy in Pharmaceutics Under supervision of Presented by Dr. Sunil Kumar Prajapati Sandeep kumar M. Pharm. (2nd Year/3rd SEMESTER ) Professor & Head Roll No:- 231255155011 INSTITUTE OF PHARMACY BUNDELKHAND UNIVERSITY, JHANSI, U.P-2024 Contents o Introduction o Drug and polymer profile o Literature Review o Research Envisaged o Objective o Plan of work o References 2  Introduction Millions worldwide experience nausea and vomiting, particularly during chemotherapy, surgery, and other medical disorders. Chemotherapy-Induced Nausea and Vomiting (CINV) affects 70-80% of individuals, with highly emetogenic chemotherapy causing 90%. Postoperative nausea and vomiting occur in 20-30% of patients, with high-risk individuals experiencing 80%. Drug administration involves various routes, including oral, parenteral, rectal, and transdermal. Oral routes are the most common, as they are easier and require less assistance. Pharmaceutical companies are considering parenteral and liquid oral dosage forms due to lower bioavailability, slow action time, and dysphagia patients. Liquid oral dosages are effective in patients like newborns, children, elderly patients, bedridden patients, and cancer patients, but face challenges in precise dosing. Traditional oral dose forms are challenging for self-administration in children, the elderly, and people with water scarcity. They also have drawbacks, such as difficulties swallowing for dysphagia, Parkinson's 3 disease, mucositis, and vomiting.  Delivery system ❖ Scientists have developed Orodiapersible Thin Film (OTF), a novel drug delivery system that dissolves in the oral cavity, avoiding the fast pass effect. These ultra-thin films, typically 50-150 μm in size, dissolve in seconds after contact with saliva. ❖ Fast-dissolving drug delivery systems are gaining popularity as novel methods to enhance safety, efficacy, and patient adherence by converting drug molecules into oral dosages. ❖ Fast-dissolving film, also known as rapid dissolving or oral thin film, is an ultra-thin, postage stamp-sized dosage form with active agents and other excipients. It offers convenience, portability, and wider acceptability for pediatric and geriatric populations. The film is manufactured as a large sheet and packaged in various formats. 4 Ideal features ▪ The oral thin film should taste good. ▪ Drug should be very moisture resistant and soluble in the saliva. ▪ It should have appropriate tension resistance. ▪ It should be ionized in the oral cavity pH. ▪ It should be able to penetrate the oral mucosa. ▪ It should be able to have a rapid effect 5  Advantage No need for water use. Safe for use without water access (e.g., during travel). No suffocation risk - Improved stability. Easy to apply. Bypasses the gastrointestinal tract, increasing bioavailability. Low dosage and low side effects. Provides rapid onset of effects for urgent conditions Improves drug absorption rate and amount. Enhanced bioavailability for less water-soluble drugs due to large surface area and rapid dissolution. 6  Drug profile: Cyclizine HCL Chemical name Cyclizine Hydrochloride (HCL Chemical formula C18H22ClN2 Molecular weight 302.8g/mol Color form Crystals from petroleum ether Odor odorless or nearly odorless Melting point 291–293°C Half-life 20 hours Absorption within 30 minutes Cyclizine is metabolised to its N-demethylated derivative, norcyclizine, which has little antihistaminic (H1) activity compared to Cyclizine Metabolism Mechanism of action Cyclizine is a histamine H1 receptor antagonist. It blocks H1 receptors in the vomiting center and vestibular nuclei in the brain. By suppressing nausea and vomiting brought on by motion sickness and other vestibular disorders, this action lowers vestibular stimulation. 7  Polymer profile: HPMC Particulars Properties Molecular formula C56H108O30 Molecular weight 1261.4 g/mol Synonyms Hydroxypropyl methylcellulose Physical Description White to off-white powder Melting point 225 to 230 °C Boling point 1101.5 °C Storage temperature Store at room temperature (typically 20-25 °C) Solubility Soluble in water 8 Refractive index 1.52  LITERATURE REVIEW Iqbal, et al., (2023) reviewed oral drug strips or dissolving film are commonly used for thin film drug delivery. Enteric or buccal/sublingual adsorption drives the drug delivery process. The primary substance used to form the film is a hydrophilic polymer, which dissolves quickly in the mouth. As an alternative to the insignificant drug delivery system (tablet, capsule, and liquid suspensions), the tool is useful. At present, three medications have been developed: rizatriptan for migraine, monosol Rx for developing testosterone, and montelukast for dementia, asthma, and allergies. The success story did not stop with the creation of thin films for drug delivery; Johns Hopkins University undergraduate biomedical engineering students first came up with the concept for a breath freshener. Sharma et al., (2022) reviewed of delivery technologies that dissolve in the stomach, like oral dispersible Films (ODFs), simplify the process of giving medication to both the general public and specific demographic groups that have difficulty swallowing, such as the elderly and children. Modern dosage forms called ODFs dissolve and disintegrate in the mouth. Because intra-oral absorption facilitates rapid action and helps prevent first-pass effects, a lower unit dose is required to achieve the intended therapeutic effect. Dispersible films, as opposed to ODTs, dissolve and disintegrate with very little saliva moisture in less than a minute. Since water is necessary for the use of dispersible films, it can be used safely even in the 9 absence of water.  RESEARCH ENVISAGED ❖ Globally, 93,753 cases of nausea and vomiting were reported in 13 countries, with 32.7% of expectant females experiencing nausea without vomiting. NVP is prevalent in 70-80% of oncological patients undergoing chemotherapy. ❖ Motion sickness affects 30-70% of the population, with 28% of Northeast and 26% of Northwest Indians predisposed to it. Females (27.3%) are more susceptible to motion sickness. Oncological treatments like chemotherapy and radiation therapy often cause nausea and vomiting. Prescription medications like ondansetron, promethazine, and metoclopramide are used. ❖ The drug cyclizine Hcl exhibits sedative properties. It penetrates the blood-brain barrier, exerting central sedation through H1 receptor antagonism. Additionally, it demonstrates anticholinergic effects by inhibiting acetylcholine receptors and addressing nausea and vomiting. In recent studies, it has been concluded that the film of this drug is not available hence it will be a promising formulation for the treatment of nausea, vomiting, and motion sickness, and improves the patient compliance. ❖ The main reason behind making this film is that the film aims to address a significant issue while investigating novel solutions for patient care. This research is crucial as it may provide an alternative treatment that enhances patient quality of life, underscoring its relevance and importance. 10 Objectives 1. To formulate and optimize cyclizine-loaded polymer films using suitable film-forming polymers. 2. To evaluate the physical and chemical properties of the developed films. 3. To characterize the films in terms of drug release kinetics and anti-emetic efficacy. 4. To assess the overall effectiveness of the cyclizine-loaded films in managing nausea and vomiting. 11  Plan of work 1. Literature survey. 5. Scanning Electron Microscopy (SEM). A) Selection of drug 6. Preparation of oral films by using a suitable method (Solvent B) Selection of polymers Casting technique). C) Selection of suitable method 7. The following parameters were to be carried out for the prepared 2. Procurement of Drug, Polymer and excipients. oral films. 3. Pre formulation studies. A) Weight Uniformity A) Solubility B) Thickness B) pH determination C) Compatibility studies C) Folding Endurance D) U.V Spectroscopy D) Drug content uniformity test E) Construction of Calibration Curve E) Swelling Behaviour studies F) Partition Coefficient G) FTIR Spectral analysis 8. In-vitro drug release study for prepared 12 oral films. 4. Differential Scanning Calorimetry (DSC). 9. Bioequivalence of marketed product.  Placebo oral film Distilled water, Ethanol add showing bubbles Distilled water trap No bubbles show 13 Experimental work  Reference ▪ P. D. Q., & Board, P. C. E. (2002). Nausea and Vomiting Related to Cancer Treatment (PDQ®): Health Professional Version. PDQ Cancer Information Summaries [Internet]. ▪ Bhusnure, O. G., Dongare, R. B., Gholve, S. B., & Giram, P. S. (2018). Chemical hazards and safety management in pharmaceutical industry. Journal of Pharmacy Research, 12(3), 357-369. ▪ Jain, P., Gupta, A., & Darwhekar, G. (2023). A Detailed Overview on Mouth Dissolving Film. Journal of Drug Delivery and Therapeutics, 13(7), 172-176. ▪ Tomar, A., Sharma, K., Chauhan, N. S., Mittal, A., & Bajaj, U. (2012). Formulation and evaluation of fast dissolving oral film of dicyclomine as potential route of buccal delivery. International Journal of Drug Development & Research, 4(2), 408-417. ▪ Sharma, R., Joshi, D., Singh, B., & Semwal, N. (2022). A review on orodispersible film a novel approach of drug delivery system. World Journal of Biology Pharmacy and Health Sciences, 12(1), 001-011 ▪ Aggarwal, J., Singh, G., Saini, S., & Rana, A. C. (2011). Fast dissolving films: A novel approach to oral drug delivery. Int Res J Pharm, 2(12), 69-74. ▪ Rathi, V., Senthil, V., Kammili, L., & Hans, R. (2011). A BRIEF REVIEW ON ORAL FILM TECHNOLOGY. International Journal of Research in Ayurveda & Pharmacy, 2(4). ▪ Saini, P., Kumar, A., Sharma, P., & Visht, S. (2012). Fast disintegrating oral films: A recent trend of drug delivery. Int J 14 Drug Dev Res, 4(4), 80-94. Thank you