Oral Liquid. pptx

Oral Liquid.

1. Topic- Oral Liquid/ Liquid Dosages Form Presented by Hariom Jaiswal Asst. Pro. B.PH 3 rd Year Industrial Pharmacy Rajiv Gandhi College of Pharmacy Nautanwa , Maharajganj , UP 273164

2. Content Introduction of Liquid dosages form Formulation and manufacturing consideration - Syrup Elixir

3. Introduction Oral Liquid/ Liquid Dosages form Definition: Liquid dosage form defined as the active ingredients are dissolved or suspended in aqueous or non aqueous solvent (or) incorporating the drug into one of the two phases of an oil and water system. Advantages Immediately available for absorption Easy administration Easy to color, flavor, sweeten Easy to change the dose

4. Disadvantages Bulky than tablets or capsule, so difficult to carry. Less stable & Less accuracy in dose. Better Incompatibility than solid dosage form. Accident breakage of container

5. Classiction of liquid dosages form

6. Formulation consideration: The common excipients used in liquid formulation are (1) Vehicles (2) Solubilizers (3) Preservatives (4) Stabilizers (5) Organoleptic agents

7. (1) Vehicles Solvents: Base in which drugs and other excipients are dissolved or dispersed. They function by breaking of bond and reducing effective charge on ions thus increasing solute-solvent forces of attraction which are eventually greater than solute-solute and solvent-solvent forces of attraction. Eg : water, hydro-alcoholic liquid systems, polyhydric alcohols, acetic acid, ethyl acetate and buffers.

8. (2) Solubilizers: To increase the solubility of the drug pH adjustment : By addition of buffer to the formulation. Co-solvency: Weak electrolytes and non polar molecules have poor water solubility It is increased by addition of water miscible solvent in which the drug has good solubility. This process is known as Cosolvency The solvents used in combination to increase the solubility of the solute is known as Cosolvents Eg of cosolvents: Ethanol, Sorbitol, Glycerin, Propylene glycol, PVP, Ethyl lactate, 1,3 butylene glycol. Complexation: It increase solubility of drug. Eg disodium EDTA, dihydroxy ethyl glycine, citric acid. Micronization : The processes involve size reduction of drug particle 1 to 10microns either by spray drying or fluid energy mill. Ex- lactose

9. Hydrotrophy : It means the increasing the solubility of drug in water by addition of large amount of some additives. This phenomenon is closely related to complexing agent Eg : Large conc of sodium benzoate(Preservative) will increase the solubility of caffeine (3) Preservatives : Microbial contamination is major problem encountered by aqueous based liquid dosage forms. Use of preservatives becomes unavoidable in such cases to prevent the growth of micro- organisms during production and over storage time. Ex- Sodium Benzoate.

10. (4) Stabilizers Physical stability : A stable formulation retains its viscosity, color, clarity, taste and odour throughout its shelf life Color can be measured spectrophotometrically. Chemical stability: It is low risk in homogeneous system than heterogeneous system. Techniques for prediction the chemical stability are well defined

11. Antioxidants : It is act as chain terminators where it reacts with free radicals in solution to stop the free-radical propagation cycle. Antifoaming agents: the formation of foams during manufacturing processes or when reconstituting the liquid dosage forms can be undesirable and disruptive. Antifoaming agents are effective at discouraging the formation of stable foams by lowering surface Suspending and Viscosity Enhancing Agents: Eg : clays, natural gums, synthetic gums In many formulations these excipients are employed in combination for enhanced effects. Humectants: these are hygroscopic substances that help to retard evaporation of aqueous vehicles from dosage forms.

12. (5) Organoleptic properties Sweetening agents: Sucrose enhances viscosity of liquids and also gives a pleasant texture in the mouth. The term sugar free solution include sweetening agents such as sorbitol, mannitol, saccharin and aspartame as alternative to sugar such as sucrose, fructose. Coloring agent: A distinction should be made between agents that have inherent color and those that are employed as colorants. Colors used in liquid dosage form must be certified by FDA as per D&C Act 1940. Certain agents- sulphur (yellow), riboflavin (yellow), cupric sulfate (blue) etc

13. Manufacturing consideration- The manufacturing process for liquid preparations for oral use should meet the requirements of Good Manufacturing Practice (GMP). The following information is intended to provide broad guidelines concerning the critical steps to be followed during production of liquid preparations for oral use. In the manufacture of liquid preparations for oral use, measures are taken to: • ensure that all ingredients are of appropriate quality • minimize the risk of microbial contamination • minimize the risk of cross-contamination

14. Steps of Liquids Manufacturing Process 1. Planning of Material Requirements : Raw Materials : Incoming raw materials should be tested as per specifications that is identity, purity, uniformity and microbial contamination . Equipments : The following types of equipments may be used in the manufacture of liquid formulations: Mixing tanks (SS 316 Stainless Steel) equipped with an agitator. Measuring devices for large and small amount of solids and liquids. A filtration system e.g. filter press Cleaning of equipments all equipments must be thoroughly cleaned and sanitized before use. Disinfectants used: Dilute solutions of H2O2, phenol derivatives. Sterilized by: Alcohol, boiling water, autoclaving, steam or dry heat.

15. 2. Liquid Preparation : Research and development of protocols concerning liquid compounding; scale - up of the bulk product compounding; physical plant control and maintenance; equipment maintenance and renovation; continuous training of personnel and personnel compensation plan; and supervision of system reports. 3. Filling and Packing : Research and development of protocols concerning filling and packing; scale-up of the finished drug product filling and packing; physical plant control and maintenance; equipment maintenance and renovation; continuous training of personnel and personnel compensation plan; and supervision of system reports.

16. 4. Sales of Drug Products : Research and development of protocols concerning product storage; distribution process; continuous training of personnel and personnel compensation plan; and supervision of system reports. 5. Vendor Handling : Research and development protocols concerning precautions to maintain product stability; control of vendor stock; and sales system reports. 6. Customer Service : Research and development of protocols concerning home storage and handling to maintain product stability; relations with health insurance companies and health care professionals; educational materials for patient counseling; and customer service system reports.

17. Syrup Introduction: Syrups are concentrated aqueous preparations of a sugar or sugar substitute with or without flavoring agents and medicinal substances. Types of Syrups: Simple syrup Medicated syrups Non-medicated syrups

18. 1. Simple Syrups: A simple syrup contains only sucrose and purified water (e.g. Syrup USP). Saturated sugar solution without flavor or medicine. Concentration of Syrup: According to B.P: 67.7% W/W According to USP: 85% W/V

19. 2. Medicated Syrups Syrups containing therapeutic agent are called medicated Syrups. Eg : Paracetamol syrup - Analgesic and Antipyretic, Sodium Valproate syrup – Anticonvulsant.

20. 3 . Non-Medicated Syrups Syrups containing flavoring agents but not medicinal substances are called non-medicated or flavored syrups” Ex- Coca Syrups. Orange Syrup etc. Use: These syrups are to serve as pleasant tasting vehicle for medicinal substances to be added in the preparation of a standard formula for a medicated syrup.

21. COMPONENTS OF Syrup Most syrups contain the following components in addition to the purified water and any medicinal agents present: (a)Sweetening Agent- the sugar, usually sucrose, or sugar substitute used to provide sweetness and viscosity (b) A ntimicrobial Preservatives (c) Viscosity Modifier (d) Flavorants (e) C olorants many types of syrups, especially those prepared commercially, contain special solvents , solubilizing agents , thickeners , or stabilizers.

22. PREPARATION OF Syrup There are four methods. Based on the physical and chemical properties on the ingredients, the choice of the method is selected- Solution with heat Agitation without heat Addition of sucrose to liquid medicament Percolation method

23. 1. Solution with heat- temperature of purified water is increased to 80 to 85 C taken off from the heat source Then add sucrose and shake it thoroughly Those substances that are heat sensitive and volatile agents are added after the solution attain the room temperature during heating, the sucrose gets hydrolysed , results in the formation of dextrose and fructose these two sugars together called as invert sugar and the process is known as inversion The inversion leads to darkening of the solution

24. 2. Agitation without heat -   vessel is taken generally made up of stainless steel or glass The vessel should be larger than the desired volume of syrup required Then the ingredients according to the formulation are added to water and mixed It is better to dissolve solid ingredients in the water first and then to add them to syrup This results in easy mixing as sugar solution generally retards mixing

25. 3. Addition of sucrose to liquid medicament-   This method is generally used for fluid extracts. But those substances which are soluble in alcohol will precipitate out as soon as the addition of water An alternation is to first dissolve all the ingredients in water Now after sometime all the precipitates formed are filtered out Now add sucrose But this method is of no use if the precipitates formed has active ingredients

26. 4. Percolation method- the principle of percolation is used A sucrose bed is prepared and then water or vehicle containing therapeutic agent is passed Here the sucrose bed should be coarse and shape of percolator must be cylindrical or cone shapped

27. Elixirs: Elixirs are , clear, sweetened, flavored, hydro-alcoholic solutions intended for oral Use and are usually flavored to enhance their palatability.” Alcoholic content vary from 10% to 12% and up to 40%. Type of Elixir: Medicated Elixir Non- Medicated Elixir

28. 1. Medicated Elixir Medicated elixirs are a solution of the active ingredient dissolved in water and an alcohol often along with other excipients such as preservatives. Mostly single therapeutic agent is present E.g : Antihistaminic Elixir - Diphenhydramine HCl, Analgesic Elixir - Acetaminophen , Cardiotonic Elixir - Digoxin

29. 2. Non- medicated elixir These are simple elixirs that do not contain medicated agents. Non medicated elixirs may be useful to the pharmacist in following ways:- The addition of a therapeutic agent to pleasant tasting vehicle Dilution of an existing medicated elixir. These only contain Water alcohol sweetening agent coloring agent

30. Need of elixir Some drug are insoluble in water so in this case we can’t use syrups & suspension. So we have to make a dosage form which could dissolve non polar compounds Aid in masking the unpleasant taste of the active ingredients.

31. Advantage of Elixir Elixirs containing 10-12% alcohol are self-preservative. Better able to maintain both water-soluble and alcohol-soluble components in solution. Has stable characteristics. Easily prepared by simple solution. Easily administered in patients having problem of swallowing solid dosage form. Used as a vehicle. Used for dilution of medicated elixirs.

32. Disadvantage of elixir Less effective than syrups in masking taste of medicated substances. Contains alcohol, can be vicious to children and adults who avoid alcohol. Because they contain volatile materials, it must be stored in a air-tight screw-top jar to avoid their escape. Needed to keep away from sources of ignition.

33. Component of elixir Alcohol Sweetening agents Water Propylene glycol flavorants

34. Method of preparation Elixirs are usually prepared by simple solution with agitation and/or by admixture of two or more liquid ingredients. Alcohol-soluble and water-soluble components are generally dissolved separately in alcohol and in purified water, respectively. Then the aqueous solution is added to the alcoholic solution to maintain the highest possible alcoholic strength at all times so that minimal separation of the alcohol-soluble components occurs. When the two solutions are completely mixed, the mixture is made to volume with the specified solvent or vehicle.

35. Process Involved in Syrup and Elixer Packaging – Empty Bottles are rinsed though Air-jet cleaning After complete cleaning, bottles are tested & transferred ahead for filling Filling machines with their automatic piston fills the bottles with accurate volume of syrup Capping is done on bottle through capping machines Plastic or aluminum capsules are bound over the neck of the bottle for secure sealing Important details regarding packaging date & expiry date are printed on bottles

36. Packaging of Syrup and elixir Syrup , as a pharmaceutical product requires safe, secure and tamper-proof handling while packaging. Packaging of syrups needs to ensure complete protection from contamination and microbial growth. Our inevitable packaging support assures the safe and secure packaging of syrups so as to ensure their extended shelf life. The general process: Filling Sealing Capping Coding & labeling Wrapping

37. Flow chart for Oral liquid packaging: Bottle washing Filling Cap sealing Inspection Turn table Outer labeling Inkjet print Checking Cap printing Labeling Checking & Stacking

38. Storage: All the products dispense extemporaneously require some form of additional storage instructions to be detailed on the label. This information can be the addition of just a product expiry date through to a number of important additional label Labeling: Every pharmaceutical preparation requires a label to be produced before the product can be dispensed or sold to patient. The accuracy of the label is of paramount importance as it conveys essential information to the patient on the use of preparation.

39. Difference between Syrups And Elixirs: Syrups Elixirs Alcohol is not necessary component more sweet than elixir more viscous than elixirs High concentration of sugar Less Stable Difficult to formulate than elixirs May not be clear formulations Sucrose Syrup can not be used for diabetic patient but if used exercise care. Alcohol is necessary component Less sweet than syrup Less viscous than syrup Less proportion of sugar More stable Easy to formulate than syrups 7.These are clear formulations 8.Can be used for Diabetic patients easily

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