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Drug excipients interaction and stability testing

The document outlines the interactions between drugs and excipients, emphasizing their roles in pharmaceutical formulations and the potential chemical and physical interactions that can affect drug stability and bioavailability. It details various categories of excipients, mechanisms of interaction, analytical techniques for detecting these interactions, and the importance of stability testing to ensure drug efficacy. The document serves as an overview for understanding how excipients impact the therapeutic effectiveness and stability of medication.

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DRUG EXCIPIENT INTERACTION 18/09/2022 1 Presented By :- Mr. Akash Vikal M.Pharmacy-1st Year Department :- Pharmaceutics I S F COLLEGE OF PHARMACY
CONTENT ➢Introduction ➢Mechanism of drug excipient interaction ➢Analytical techniques used to detect drug excipient interaction ➢Kinetic of drug stability ➢Stability testing 2
INTRODUCTION ➢ Excipients are ingredients which along with active pharmaceutical ingredients make up the dosage forms. ➢ Excipients act as protective agents, bulking agents and can also be used to improve bioavailability of drug. ➢ An pharmaceutical excipient is a pharmacologically inactive substance formulated alongside the API of a medicine to impart specific quality of them. 3
Role of excipients- ➢ Provide bulk to the formulation. ➢ Protect, support or enhance the stability of formulation. ➢ Improve bioavailability of drug. Ideal properties of excipients- ➢ No interactions with drug ➢ Feasible ➢ Cost effective ➢ Pharmacologically inert ➢ Stable for handling 4
Excipient are inactive ingredients said as carriers for the active ingredients in a pharmaceutical product. These maybe classified into the following categories:- • Binders • Disintegrants • Fillers (diluents) • Lubricants • Glidants • Compression aids • Colors • Sweeteners • Preservatives • Flavors • Coatings/film formers • Suspending/dispersing agents/surfactants • Anti-adherents • Sorbents • Anti-oxidants • Buffering agents • Chelating agents • Viscosity imparting agents • humectants 5
Drug excipient interaction ➢Drug substances are usually in intimate contact with excipient. Although these are pharmacologically inert, they are undergo chemical and physical interaction with drug substance under favourable condition. These interactions can lead to instability resulting in the formulation of new entities. 6
Importance of these studies ➢To find out how compatible an excipient is with API. ➢Maximizes the stability of a dosage form. ➢Do not have impact on stability of API. ➢Determine the list of excipients that can be used in final dosage form. ➢Helps to avoid surprise problem during formulation process. ➢These studies are the part of preformulation study. 7
Mechansim of drug excipient interaction ❑ They can be classified as :- ➢ PHYSICAL INTERACTIONS ➢ CHEMICAL INTERACTIONS ➢ BIOPHARMACEUTICAL INTERACTIONS ➢ EXCIPIENT – EXCIPIENT INTERACTIONS 8
Physical interactions- ➢Physical interactions alter the rate of dissolution, dosage uniformity, etc. ➢Physical interactions do not involve chemical changes, thus permitting the components in the formulation to retain their molecular structure. ➢Physical interactions are difficult to detect. Interaction complexation- ➢Usually binds reversibly with drug to form complex. ➢Insoluble complexes are formed which lead to slower dissolution. ➢Decreased absorption of drug. 9
Beneficial effect example ➢Cyclodextrin is often used to improve bioavailability of poorly water soluble drugs. ➢This increases bioavailability and increases rate. Detrimental effect example ➢Tetracycline formed insoluble complex with calcium carbonate leading to slower dissolution and decreased absorption. 10
Chemical interactions ➢ Active pharmaceutical ingredients and excipients react with each other to form unstable compounds. ▪ Stability under high humidity conditions:- ➢ In presence of moisture, many drug substances hydrolyze react with other excipients or oxidize. ➢ These tests are performed by exposing the drug to different relative humidity conditions. 11
Biopharmaceutical interactions ❑ These are the interactions which are observed after administration of medicine. These interactions occur in the form of - ❖ The interaction is between the medicine ( drug substance and excipients ) and the body fluids. ❖ The interactions have the tendency to influence the rate of absorption of the drug. Various example of these interactions are as follow :- ❑ Premature breakdown of enteric coat ❑ Increase in gastrointestinal motility ❑ Effect on P-glycoprotein efflux transporter 12
Premature breakdown of enteric coat- ➢ Enteric coating polymers e.g.,cellulose acetate phthalate and hydroxyl propyl cellulose acetate phthalate. ➢ Dissolve prematurely in the stomach in the presence of antacids or drugs. ➢ Cause increase in the ph of the stomach. ➢ Cause premature release of API in stomach itself, which results in degradation of drug in stomach. e.g.,side effects like gastric bleeding as in the case of NSAIDs. 13
Increase in gastrointestinal motility ➢ Many excipients such as sorbitol have the tendency to increase gastrointestinal motility, thus reducing the available time for absorption of drugs like metoprolol. Effect on P-glycoprotein efflux transporter ➢ P-glycoprotein thus interferes in the bioavailability of different anticancers and other drug substances. Thus, several excipients e.g., span 20, tween 20, tween 80, pluronic, poloxamer, etc., are incorporated in the formulations which help in inhibition of P- glycoprotein to enhance availability of the drug into the cell, to produce the desired action. 14
Analytical techniques used to detect drug-excipients interaction:- ❑ Thermal methods - ❖ DSC-differential scanning calorimetry ❖ DTA-differential thermal analysis ❖ Isothermal micro calorimetry ❖ Hot stage microscopy ❑ Spectroscopic techniques - ❖ FT-IR spectroscopy ❖ Powder X-ray differaction ❖ Solid state NMR 15
❑Chromatography- ❖ TLC-thin layer chromatography ❖ HPLC-high performance liquid chromatography ❑ Accelerated stability study- ❑Miscellaneous- ❖ Radiolabelled techniques ❖ Fluorescence spectroscopy 16
Drug kinetics ➢ Definedas how drug changes with timeeither study of rate of changes. ➢ Many drugs are not chemicallystable and the principle of chemical kinetics are used to predict the timespan for which a drug will remain maintain its therapeutic effectiveness or efficacy at a specified temperature. ❑ Importance of studying kinetics- it determines:- ➢ Stability of drug/half life of drug:-defined as time necessary for a drug to decay to its half life or 50% conc. (e.g.,100% - 50%, 50% - 25%). ➢ Shelf life:-definedas the timerequired for a drug to decay to 90 17
Rate and order of reaction ❑ The Concentration of drug which influences the rate of reaction or process is called its order of reaction ❑ The two commonly encountered rate processes are:- ❖ ZERO ORDER REACTION ❖ FIRST ORDER REACTION 18
FIRST ORDER REACTION ➢ These are the reactions whose rate is directly proportional to concentration of the drugs undergoing reaction I.e., greater the concentration, faster the reaction. ZERO ORDER REACTION ➢ Also called as constant rate process. ➢ The rate of reaction is independent of concentration either rate of reaction connot be increased further by increasing the concentration of reactant. 19
Factors affecting rate of reaction ❖ Temperature ❖ Light ❖ Solvent ❖ Phase and surface area ❖ Catalysis ❖ Concentration Kinetic of drug decomposition ❖ Hydrolysis ❖ Oxidation ❖ Photolysis ❖ Racemization 20
Stability testing ❑ Stability : defined as capability of a particular formulation in a specific container/closure system to remain within its physical, chemical, microbiological, toxicological, protective and informational specifications. ❑ It is the extent to which a product retains, within the specified limits, throughout its period of storage and use, the same properties and characteristics possessed at the time of its packaging. 21
Scope of stability testing ❖ Provide evidence as to how the quality of drug product varies with time. ❖ Establish shelf life of drug product. ❖ Determines recommended storage conditions. ❖ Determine container closure system suitability. Stability testing methods ❖ Real time stability testing ❖ Accelerated stability testing ❖ Retained sample stability testing ❖ Cyclic temperature stress testing 22
Importance of stability testing ❖ Assurance to patient that drug is safe. ❖ Legal requirement to provide data. ❖ To protect the reputation of the manufacturer. ❖ To provide a database. ❖ To determine shelf life and storage conditions. ❖ To verify that no changes have been introduced in the formulation or manufacturing process that can adversly affect the stability of the product. 23
Type of stability ❖CHEMICAL:- Each activeingredientsretains its chemical integrity and lebelled potency within specifiedlimits. ❖PHYSICAL:- Includes appearance, palatability, uniformity, dissolution and suspend abilityare retained. ❖MICROBIOLOGICAL:-Sterility or resistance to microbial growth is retained according to specificrequirements. ❖THERAPEUTIC:- Activity remains unchanged. ❖TOXICOLOGIC:- No significant increase in toxicity. 24
References ❖Lachman and lieberman, the theory and practice of industrial pharmacy. ❖N.Fathima, kajal ahir, vandana patel, lata manani, chirag patel drug excipients interactions and its importance in dosage form development, journal of applied pharmaceutical science 2011. ❖Priyanka patel, kajal ahir, vandana patel, lata manani, chirag patel drug-excipient compatibilty studies: First step for dosage form development, The pharma innovation journal 2015. ❖P.J. Crowly and L.G. Martini,"excipients in pharmaceutical products" Encylopedia of pharmaceutical technology(Marcel Dekker Inc. New york, USA. ❖Banker and Rhodes, modern pharmaceutics, Marcel Dekker Inc. 2002. Thankyou..... 25