Drug excipient interaction drug excipient interaction occurs between the api and excipient materials. We propose the use of itc to assess the relative strength of drugexcipient and drugs selfassociation binding interactions. Unintended physicochemical interaction of an excipient with a drug substance in a dosage form can result in the complexation or binding of the drug, resulting in slow andor incomplete drug release in a dissolution medium. The components of the drug product retain their chemical structure but undergo changes which alter their physical properties. Individual drugs sample 14, individual excipients sample 57 and drug drug drug. Many of the reported drugexcipient reactions involve hydrolysis, oxidation, or specific interaction of drugs with reactive impurities in excipients. Drug excipient compatibility study using thermal and nonthermal methods of analysis.
This paper focuses on drugexcipient interactions in. Societys modern college of pharmacy for ladies, borhadewadi, atpost moshi, talhaweli, dist pune, maharashtra. Drug drug and drug excipient interactions can occur before or after admin pharmacokinetic modification of active drug after modification can change its pharmacological effect not enough drug will be absorbed in bloodstream or toxicity from accumulation in the plasma interactions that take place before admin are considered incompatibilities. Special precautions for storage at ambient temperature under dry conditions and away from direct sunlight. Dsc is a commonly used method to identify the drug excipient interactions and to determine the thermal stability of drug or drug excipint mixtures. However, these techniques are often applied after weeks and months of oven aging under varying conditions of temperatures and or humidity. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drugs and, consequently, their therapeutic efficacy and safety. Chemical incompatibility therapeutic incompatibility it is the modification of the therapeutic effect of one drug due to the prior concomitant administration of another, or it may occur due to overdose or wrong dose of the drug being.
Pharmacokinetic properties if used as directed, it is not normally absorbed. Drugdrug and drugexcipient interactions can occur before or after admin pharmacokinetic modification of active drug after modification can change its pharmacological effect not enough drug will be absorbed in bloodstream or toxicity from accumulation in the plasma interactions that take place before admin are considered incompatibilities. Drug incompatibility pharmaceutical incompatibility of a drug refers to interactions between two or more substances which lead to changes in chemical, physical and therapeutic properties of the drug or its dosage form. Any physical or chemical interaction between drug and excipient can affect bioavailability and stability of drug. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients. Examples of active drugexcipient interactions, such as transacylation, the maillard browning reaction, acid base reactions and physical. Impact of excipient interactions on drug bioavailability from. The incompatibility between a drug and an excipient and that which occurs between a drug and moisturewater activity due to the ability of the excipient to absorb moisture, represents two different kinds of incompatibilities. Nature and content of container bulk tanker approx. Assessment of possible incompatibilities between the drug and different excipients is an important part of preformulation. The model active pharmaceutical ingredients apis under study are. Differential scanning calorimetry dsc is one of the welldeveloped techniques used in detection of incompatibilities in drug drug and drugexcipient interactions.
Differential thermal analysis dta is similar to dsc in many respects and analogous information about the same range of thermal events can be observed. Pdf interactions and incompatibilities of pharmaceutical. Isothermal stress testing method is used to assess the compatibility of drugdrugdrugexcipient. These types of interactions are quite common but are very difficult to detect in dosage forms. Interactions and incompatibilities of pharmaceutical. Excipient development for pharmaceutical, biotechnology. This paper focuses on drug excipient interactions in solid dosage forms that. This delay in detecting drugexcipient incompatibility is expensive and can significantly impact commercialization of a beneficial drug. Characterization of drug excipient compatibility christin t. The most widely used techniques to verify incompatibilities between the drug and excipient are the thermal analysis. Case studies and overview of drug degradation pathways, authorkishore kumar hotha and swapan roychowdhury and veerappan subramanian. Drug excipient compatibility testing protocols and.
Drug excipient interaction in pharmaceutical dosage forms the active pharmaceutical ingredients are in intimate contact with the excipient which are greater quantity excipient and drugs may have certain incompatibility which lead to drug excipient interaction. These interactions adversely affect the therapeutic efficacy, safety, and appearance of the. Impact of excipient interactions on drug bioavailability. Nov 17, 2017 drug excipient interaction in pharmaceutical dosage forms the active pharmaceutical ingredients are in intimate contact with the excipient which are greater quantity excipient and drugs may have certain incompatibility which lead to drug excipient interaction. The incompatibilities with the functional groups shall be kept in m ind while eva. Drugexcipient interaction and its importance in dosage. Pharmacy phaqa11 256212885054 malla reddy college of pharmacy under the guidance of mrs. Drug interactions and incompatibilities sciencedirect. The preformulation screening of drugexcipient interaction requires 1.
Abstract in recent years there has been an increasing interest in the study of drugexcipient interactions in pharmaceutical dosage forms. Certain amine drugs paracetamol react with lactose diluent in the presence of magnesium stearate to form brown color compound. Studies of drugexcipient compatibility represent an important phase in the preformulation stage for the development of all dosage forms. Drugexcipient interactions sometimes lead to incompatibility via decomposition and degradation of drug or via conversion of a drug into less active form. The discovery of a new chemical entity with promising efficacy and toxicity is. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. The final step in terminating drug action is elimination from the body.
The incompatibilities between drug and excipient are reflected. Individual drugs sample 14, individual excipients sample 57 and drugdrugdrugexcipient. The chemical nature of the excipient, drug to excipient ratio, moisture, micro environmental ph of the drug excipient mixture, temperature, and light, on dosage form stability could be the possible factors for the drug degradation process and the formation of the reaction products. Dsc is a commonly used method to identify the drugexcipient interactions and to determine the thermal stability of drug or drugexcipint mixtures. Incompatibilities of pharmaceutical excipients with active. The ideal excipients must be able to fulfill the important. They suggest types of excipients that are suitable for various dosage forms and what to do. Jan 01, 2010 abstract in recent years there has been an increasing interest in the study of drug excipient interactions in pharmaceutical dosage forms. The kidneys are the major organs of excretion of most drugs, but the liver, lungs, and intestines may play a role in drug elimination. Differential scanning calorimetry this technique involves the measurement of solid state transitions due to interaction between api and excipient approximately 2 mg of the pure drug and excipient are used to take dsc example. A general mechanistic understanding of the basis of these interactions is essential to design robust drug products. Isothermal stress testing method is used to assess the compatibility of drug drug drug excipient. Understanding properties and mechanisms that govern drug degradation in the solid state is of high importance to ensure drug stability and safety of solid dosage forms. Thermal analysis as a useful tool in drugexcipient.
May 19, 2012 excipients are generally pharmacologically inert, but can interact with drugs in the dosage form and the physiological factors at the site of absorption to affect the bioavailability of a drug product. Drugexcipient interaction and incompatibilities sciencedirect. Excipients and drugs may have certain incompatibilities which lead to drug. Maillard reaction is one of the most important and well known drugexcipient interactions which is studied by many researchers in drugs containing at least one amine functional group. The preformulation screening of drug excipient interaction requires 5 mg of drug, in 50% mixture 1. Risk prevention in infusion therapy drug incompatibility. Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Incompatibilities of pvp with lansoprazole, famotidine and atenolol all indicate that its carbonyl group is pivotal to degradation reactions. Pharmaceutical dosage form is a combination of active pharmaceutical ingredients api and excipients.
Pdf drugexcipient interaction and incompatibilities. Examples of active drug excipient interactions, such as transacylation, the maillard browning reaction, acid base reactions and physical. Solid state interactions between ketoprofen and excipients. Excipients are generally pharmacologically inert, but can interact with drugs in the dosage form and the physiological factors at the site of absorption to affect the bioavailability of a drug product.
It is important to assess the risk whether such interactions would reduce oral bioavailability of a drug from its dosage form. This delay in detecting drug excipient incompatibility is expensive and can significantly impact commercialization of a beneficial drug. Evaluation of physicochemical incompatibilities during parenteral drug administration in a paediatric intensive care. According to international confederation of thermal analysis ictac and iupac, thermal analysis is a term that encompasses. Drugexcipient interaction drugexcipient interaction occurs between the api and excipient materials. The potential physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability.
Solid state interactions between ketoprofen and excipients in. Drug substances and excipients interact without undergoing changes involving breaking or formation of new bonds. Jan 26, 2016 there are three types of drug incompatibilities 1. Mixture should be examined under n 2 to eliminate oxidative and pyrrolytic effects at heating rate 2, 5 or 100 c min on dsc apparatus. Physical interactions can affect rate of dissolution, uniformity of dose or ease of administration. Pdf on jan 1, 2018, bapi gorain and others published drugexcipient interaction and incompatibilities find, read and cite all the research you need on researchgate. Sep 20, 2015 unintended physicochemical interaction of an excipient with a drug substance in a dosage form can result in the complexation or binding of the drug, resulting in slow and or incomplete drug release in a dissolution medium. This is hardly surprising interactions in solution. Studies of drug excipient compatibility represent an important phase in the preformulation stage for the development of all dosage forms. Differential scanning calorimetry dsc is one of the welldeveloped techniques used in detection of incompatibilities in drug drug and drug excipient interactions. Drugexcipient interaction and its importance in dosage form. A new approach to the measurement of drugexcipient.
The preformulation screening of drugexcipient interaction requires 5 mg of drug, in 50% mixture 1. Feb 07, 2014 drug drug drug excipient compatibility study. Characterization of drugexcipient compatibility christin t. A number of techniques can be used to indicate the drug excipient interaction. Excipient interactions and best practice guide for use of excipients and types of interactions possible in different dosage forms chapters 8,1019. Recent developments in the understanding of the degradation pathways further impact methodologies used in the pharmaceutical industry for potential stability assessment. These interactions adversely affect the therapeutic efficacy, safety, and appearance of the active constituent tekade et al. Drug excipients interaction can either be beneficial or detrimental, which can be simply classified as. Drug excipient interaction1519 in pharmaceutical dosage forms the active pharmaceutical ingredients are in intimate contact with the excipients which are in greater quantity. Introduction nation of active pharmaceutical ingredients api absorption crowley and martini. Mixture should be examined under n 2 to eliminate oxidative and pyrrolytic effects at heating rate 2, 5 or 100c min on dsc apparatus. The obtained informations are useful to establish the suitable drug formulation technology and the storage conditions.
Packageexcipient interactions these interactions are discussed in detail as follows. Sep 27, 2011 drug degradation in products often results from the reaction of active pharmaceutical ingredients api with excipients used in the formulation. Physical interactions are frequently used in manufacturing of dosage form, for example to modify drug dissolution. Drugdrugdrugexcipient compatibility studies on curcumin. The formulation of a drug substance frequently involves it being blended with different excipients to improve manufacturability, and to maximize the products ability to administer the drug dose effectively. Depending on the application of a specific excipient as well as other formulation and processing factors, the presence of these reactive impurities in excipients even in trace amounts could influence the safety and efficacy of the drug products, especially for highly potent apis which have low dose and high excipientapi ratio in the drug product. Maillard reaction is one of the most important and well known drug excipient interactions which is studied by many researchers in drugs containing at least one amine functional group. Drug excipients interaction tablet pharmacy silicon dioxide.
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