Orally Disintegrating Strips

Emerging Trend to Alternate the Drug Delivery System

1. Orally Disintegrating Film Emerging Trend to Alternate the Drug Delivery System

2. What is Drug ? Routes OF Administration..!! Different dosage forms…!!! Condition ..? ODF…!!!! Products..!!!

3. What Is Drugs Natural or  synthetic substance which (when taken into a living body) affects its functioning or structure, and is used in the diagnosis, mitigation, treatment, or  prevention of a disease or relief of discomfort. Also   called legal drug or medicine. A  legal or medicinal drug (such as Paracetamol, Aspirin), however, can be harmful and addictive if misused.

4. ROUTES OF DRUG ADMINISTRATION

5. What are the Dosage forms Depending on the method/route of administration, dosage forms come in several types. Oral Pill, i.e. tablet or capsule Specialty tablet like buccal, sub-lingual, or orally-disintegrating Thin film (e.g .,  Mouth dissolving films) Liquid solution or suspension (e.g.,  drink or  syrup) Powder or liquid or solid crystals Natural or herbal plant, seed, or  food of sorts (e.g., marijuana such as that found in "special brownies") Pastes (e.g., Toothpaste) Parenteral Intradermal (ID) Intramuscular (IM) Intraosseous (IO) Intraperitoneal (IP) Intravenous  (IV) Subcutaneous (SC ) Intrathecal (IT) Injection into the spinal column Drug delivery  refers to approaches, formulations, technologies, and systems for transporting a  pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect

6. Suppository Vaginal (e.g., douche,  pessary , etc.) rectal Urethral suppositories Nasal suppositories Ear cones Inhalational Aerosol Inhaler Nebulizer Vaporizer Topical Cream,  gel,   liniment or  balm, lotion, or ointment, etc. Ear drops ( otic ) Eye drops (ophthalmic) Skin patch (transdermal ) Vaginal rings Route of Drug Administration Delay time for Action Intravenous route 30-60 seconds Intraosseous route 30-60 seconds Endotracheal inhalation 2-3 minutes Sublingual route 3-5 minutes Intramuscular route 10-20 minutes Rectal route 5-30 minutes Ingestion 30-90 minutes

7. Old Person(Angina pectoris) Travelling to some place Don’t have water No Doctor around him He has only conventional drug “ tablet of verapamil” What he’ll Do ? Condition …?

8. Oral/Buccal Cavity

9. Oral Route Of Administration and Development of Oral Disintegrating Film Technology

10. O ral Route is most preferred route of administration by Manufacturers and Medical Practitioners. A bout 60% of all dosage forms available are the oral solid dosage form. The lower bioavailability , long onset time and dysphagia patients turned the manufacturer to the parenteral and liquid orals . B ut the liquid orals (syrup, suspension, emulsion etc.) have the problem of accurate dosing mainly and parenteral are painful drug delivery, so most patient incompliance .

11. Conventional Tablets Modified Released Capsules Fast Dissolving Tablets/Caps. Orally Disintegrating Films. 3 Factors for Development Convinience Bioavailibity Rapid onset of action Maximum efficacy

12. The ODFs place as an alternative in the market due to the consumer’s preference for a fast dissolving product over conventional tablets / capsules. The oral thin-film technology is still in the beginning stages and has bright future ahead because it fulfils all the need of patients Eventually , film formulations having drug/s will be commercially launched using the oral film technology . However, for future growth point of view the oral thin film sector is well-positioned A/q to Technology catalyst and Root analysis firms --- $500M to $2 billion Orally Disintegrating Films These approved Rx films, have potential to dominate over other oral dosage forms of the same drugs. It seems that the value of the overall oral thin film market will grow significantly . In US market the OTC films of pain management and motion sickness are commercialized. More importantly, prescription OTFs have now been approved in US, EU and Japan which are the three major regions.

13. Anatomy

14. 1:  Stratum basale 2:  Stratum spinosum 3:  Stratum granulosum 4:  Stratum corneum Histology of buccal cavity Total Surface area of oral cavity is 100cm 1/3 are covered with epithelium layer 2 types of layers exist 1. Keratinized (Ceramides) 2. Non- Keratinized ( polar lipids, particularly cholesterol sulphate and glucosylceramides)

15. Delivery system is simply place Film on Tongue or in Buccal cavity Instantly wet by saliva (Due to Hydrophilic agent present in film ) Hydrated film dissolves and release medication/ active constituent And would be available for oromucosal absorption. Mechanism of action

16. Mucoadhesion Saliva : 99% of water, 1% of Protein and Carbohydrate, (0.5 to 2litres) Stages Contact Stage 1. Formation of Bond (Mucoadhesive Molecule + Glycoprotien) 2. Consolidation stage Solution(Drug+ Mucus) is ready to absorb

17. The absorption potential of oral mucosa is influenced  by  The   lipid  solubility  and therefore the permeability of the solution (osmosis);  The  ionization  (pH);  T he   molecular weight  of the substances.  For   example ,  absorption  of  some  drugs  via  oral  mucosa  is  shown  to  incr - ease   when  carrier  pH  is  lowering  (more  acidic)  and  decrease with  a lowering of pH (more alkaline)  Absorption Trans cellular (Across the biological Membrane) Para cellular (Intercellular space)

18. Bioavailability The   administration via ODF   was  found  to  provide   rapid  relief  of  symptoms , with  first‐ p ass  metabolism.  The  extent of  first- pass  metabolism  decreased   to   48%  through buccal delivery system. Hence Increases the bioavailability by 50%.

19. Drugs………. ……………………… 5-30% w/w Water soluble polymers……………………45% Plasticizers…………………………… …. 0-20% Excipients Surfactants…………………………….. qs Sweetening agents……………….. ……3-6% Saliva stimulating agents………. ……...2-6 % Fillers, Colors, Flavors .... ……. …….. qs Composition 1-20cm 2

20. Water soluble Polymers : Pullulan , gelatin and hypromellose are most commonly used for preparation of ODF. Plasticizers : Glycerol , Propylene glycol , low molecular weight polyethylene glycols, phthalate derivatives like dimethyl , diethyl and dibutyl phthalate, Citrate derivatives such as tributyl, triethyl, acetyl citrate, triacetin and castor oil are some of the commonly used plasticizer excipients Sweeteners : Dextrose , fructose, glucose, liquid glucose and maltose. Surfactants : S odium lauryl sulfate , benzalkonium chloride, tweens Saliva stimulating agents : Citric acid, malic acid, lactic acid, ascorbic acid and tartaric acid Flavors : Any flavor (US-FDA approved) can be added , such as intense mints, sour fruit flavors or sweet confectionery flavors15

21. Drugs has been Incorporated as ODF. Antiulcer (e.g. omeprazole, ) Antiasthamatics (salbutamol sulphate) Antitussives , E xpectorants , Antihistaminics , NSAID’S(e.g. paracetamol , meloxicam , valdecoxib) Less bitter, potent and highly lipophilic drug should be preferred for ODF . Proven that the concentration level of API per dose can extend up to 50% per dose weight.

22. Advantage Disadvantage No special Set up is required for Pharma Industry Rapid disintegration and dissolution in oral cavity and promote systemic absorption of API’s (Large surface area). No need of water or spoon for administration or chewing. Dose accuracy in comparison with liquid dosage forms. Rapid onset of action. Bypass FPM (First Pass Metabolism). Lower Doses Minimal Side effects . Destructive acidic environment of stomach can be avoided. Delivery can also be terminated easily. Site specific action and Local action Noninvasive Patent Life Extension High doses cannot be incorporated into the strip. (Hence researchers have proven that the level of active can be improved upto 50% per dose weight.) Ex. Gas-X Thin strips has loading of 62.5 mg/strips Expensive Packaging of oral film.

23. Disadvantages of LDF Shorter life than other dosage form , Harder to measure accuracy, Need special storage condition Less stable , Easily affected by microorganisms, Bulky to carry around. Easy to loss by the breakage of the container . Measuring dose is required. Disadvantages of ODF Swallowing Formulation difficulties. Some drugs have poor oral bioavailability or poor water solubility. Some drugs have an irritant effect on the stomach Disadvantages of Sublingual DF. Area available for absorption is much less. Unsuitable for bitter drugs Poor Patient compliance Eating , drinking, and smoking is not allowed. Administration of highly ionic drug is not allowed. Administration of high dose is not possible Advantage of ODF’s over other dosage forms

24. Products

25. Bthyn-12 Methylcobalamine 1500mcg Indications Diabetic Neuropathy Diabetic Nephropathy CVD Fibromylgia Alzhiemers Disease Anemia Cervical Spondolytis Megaloblastic anaemia  

26. Dxthyn and Dxthyn DS Dextromethorphan 5.5mg and 11mg Indication In cough associated with Smoking and pollution Acute and chronic RTI

27. Fil zeal Tadalafil 20 mg Indication Erectile Dysfunctioning

28. Thanks…..