Towards an improved understanding of drug excipient. Introduction excipients are considered as pharmacologically inert but can initiate, propagate or participate in chemical or physical interactions with drug components, which may compromise the effectiveness of a medication. These excipients are considered pharmacologically inert and have been used since years in pharmaceutical formulations. Excipients interactions and drug degradation due to flavors, lactose, micro. Jan 29, 2016 identification of drug degradation in presence of excipients excipient impurities requires extensive knowledge and adequate analytical characterization data. Drugdrugdrugexcipient compatibility studies on curcumin. Pdf interactions and incompatibilities of pharmaceutical excipients. The magnitude of this effect will depend upon physicochemical properties of drugs as well as quantity and quality of excipients used.
The main classes are the antioxidants, coating materials, emulgents, taste and smellimprovers, ointment bases, conserving agents, consistency. Physicochemical and mechanical properties of an excipient are known to impact quality, performance, or processing of the final drug product. Pharmaceutical dosage form is a combination of active pharmaceutical ingredients api and excipients. This chapter describes the development of a methodology to assess the biorelevance of the drug release impact of drug excipient binding interactions using a model compound, brivanib alaninate. This improves patient compliance, especially in children. Interactions of it with different types of buffers were. Pdf drugexcipient interaction and incompatibilities. Last, but not least, some excipients are used simply to make the product taste and look better. Pharmacy phaqa11 256212885054 malla reddy college of pharmacy under the guidance of mrs. During the development of a given drug formulation, the interactions between the drug and excipients need to be carefully studied to ensure that the drug is stable in the formulation. The mechanisms of drug excipients interactions are not fully understood despite the best efforts of several eminent investigators in the field. Although considered pharmacological, excipients may consider a drug, due to chemical or physical interactions with the composition of the drug. Heat and water are the primary catalysts for drugexcipient interactions and play a critical role in the degradation of a drug substance.
Interactions of oral molecular excipients with breast. Reineke, departments of chemistry and department of chemical engineering and materials science, university of minnesota, minneapolis, minnesota 55455, united states. Feb 28, 2018 b interactions between drug and excipient residueimpurities department of pharmacy, adtu 10 excipients residues povidone. Machine learning uncovers excipientdrug interactions. Drug excipient interaction and its importance in dosage form development article pdf available in journal of applied pharmaceutical science 16. Measurement of rate of heat evolved or absorbed by the sample during a temperature programme. Validation confirms vitamin a palmitate as an inhibitor of pglycoprotein transport and abietic acid as an inhibitor of ugt2b7 metabolism. Here, drug is made immobilized as the sp and solution to be tested acts as mp. For locally acting drugs having systemic side effects, a proper excipient could.
In this present article, certain kinds of drugs and their interactions with the most commonly used excipients were discussed with case studies. Mechanisticunderstandingbased selection of excipients may improve formulation development strategies for generic drug products and potentially accelerate their approval. Excipients may also contain impurities or form degradation products that in turn cause decomposition of drug substances. Request pdf pharmaceutical excipients in drugdrug interaction during the development of a given drug formulation, the interactions between the drug and excipients need to be carefully. In each of these plots, a green circle represents the lowest excipient. The two commonly employed compatibility screening techniques are isothermal stress testing of binary drug excipient mixtures and thermal analysis using either dsc or differential thermal analysis dta. Interactions of it with different types of buffers were a drugexcipient compatibility studies in solid dosage forms. There has been increasing interest in the use of bioadhesive polymers as excipients in the design of drug delivery systems. Physical and chemical interactions between drugs and excipients can affect the chemical nature, the stability and bioavailability of drug products, and consequently, their therapeutic efficacy and safety 1. However, some of the common ways by which excipients may alter drug stability in a dosage form include. Studies of active drugexcipient compatibility represent an important phase in the preformulation stage of the sonali s. Pharmaceutical excipients are traditionally considered as pharmacologically inert substances, but, can also actively participate in drugexcipient interactions, viz. Some excipient interactions can be detrimental and need to be avoided. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of.
Abietic acid and gum rosin inhibit ugt2b7 metabolism ex vivo. This paper focuses on drugexcipient interactions in. Excipients also are important in parenteral formulations to assure safety antimicrobial preservatives, minimize pain and irritation upon injection tonicity agents, and control or prolong drug delivery polymers. Various excipients undergo such kind of interactions. Software checkers for drug interactions are widely available, but have limited clinical utility. Drugexcipient interaction and its importance in dosage form. However, there are few clinically relevant or significant drugdrug reactions.
Soluble and ionizable excipients can generate counter ions that interact with ionizable drug substances leading to the formation of insoluble drugexcipient products. Drug excipient interactions sometimes lead to incompatibility via decomposition and degradation of drug or via conversion of a drug into less active form. Impact of excipient interactions on drug bioavailability from. Excipients as like other active pharmaceutical ingredients need to be stabilized and standardized. Although considered pharmacologically inert,excipients can initiate, propagate or participate in chemical or physical interactions with drug. Appreciable interest is developing on the data demonstrating the role of excipients in altering the drug absorption across the intestine. In addition to that, several degradation products of the 6aminocaproic acid reacting with itself, e. Excipients are included in dosage forms to aid manufacture, administration or absorption.
Drug excipient interaction in pharmaceutical dosage forms the active pharmaceutical ingredients are in intimate contact with the excipient. The conformational flexibility and length of the hydrophobic regions of amphiphilic excipients appears to be critical for effectiveness. Excipients interactions and drug degradation due to flavors, lactose, microcrystalline cellulose, povidone, crospovidone, hydroxypropyl cellulose, stearic acid, magnesium stearate and silicon dioxide were explained. Drug interactions european journal of hospital pharmacy. Recent developments in the understanding of the degradation pathways further impact methodologies used in the pharmaceutical industry for potential stability assessment. It is important to assess the risk whether such interactions would reduce oral bioavailability of a drug from its dosage form.
The aim of this article is to identify the various processesfactors that cause the drug excipients interaction and regulatory implication of drug excipients interaction. Pdf drugexcipient interaction and its importance in. Drugexcipient compatibility studies the pharma innovation. Consistency of drug release and bioavailability stability including protection from degradation ease of administration to the target patient populations by the. Sep 20, 2015 it is important to assess the risk whether such interactions would reduce oral bioavailability of a drug from its dosage form. Studies of active drugexcipient compatibility represent an important phase in the preformulation stage of the development of all dosage forms. Drug excipients interaction tablet pharmacy silicon dioxide. Our study aimed at investigating the effects of molecular excipients present in orally administered fdaapproved drug products on the intestinal efflux transporter, bcrp abcg2, which plays a critical role in. Drugexcipient interaction and its importance in dosage form development. 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. Elimination of endothermic peak department of pharmacy, adtu 19 20. The majority of small molecule api instability reactions occur via hydrolysis, oxidation and. Drug excipients interaction can either be beneficial or detrimental, which can be simply classified as.
Many excipients have more than one use, which can be an advantage since it reduces the number of excipients needed and minimises the risk of interactions between them. Impact of excipient interactions on drug bioavailability. Excipient excipient interactions can be undesirable as well as some interactions are used in the formulations to get the desired product attributes. Feb 07, 2014 drug drug drug excipient compatibility study. The aim of this article is to identify the various processesfactors that cause the drugexcipients interaction and regulatory implication of drugexcipients interaction. The preformulation screening of drugexcipient interaction requires 5 mg of drug, in 50% mixture 1. These are all examples of positive or synergistic interactions between excipients and drugs. Drug interactions should be considered both in the differential diagnosis of symptoms for interactions that have already occurred and when prescription changes are made for potential interactions. See discussions, stats, and author profiles for this publication at. Zhong, evan crane, chihhsin lin, robert langer, giovanni traverso.
Pdf drugexcipient interaction and its importance in dosage form. Drugexcipients interactions and compatibility study. Drugexcipient interaction and its importance in dosage form development nishath fathima, tirunagari mamatha, husna kanwal qureshi, nandagopal anitha and jangala venkateswara rao excipients are included in dosage forms to aid manufacture, administration or absorption. Properties of excipients generally show different degrees of inherent or natural variability due to variations of the starting materials and manufacture of the excipients. Interactions and incompatibilities of pharmaceutical. Drugdrug interactions are very common and many thousands are described in standard prescribing reference books. Individual drugs sample 14, individual excipients sample 57 and drugdrugdrugexcipient. The central role of excipients in drug formulation european. Pdf on jan 1, 2018, bapi gorain and others published drugexcipient interaction and incompatibilities find, read and cite all the research. Careful selection of the excipients thus is very important. Pdf drugexcipient interaction and incompatibilities researchgate. Apr 18, 20 excipients play a central role in the drug development process, in the formulation of stable dosage forms and in their administration.
Isothermal stress testing method is used to assess the compatibility of drug drug drug excipient. This hypothesis was supported by molecular modeling studies to better understand the interactions between the excipients with the drug nanoparticle surface. Excipients act as protective agents, bulking agents and can also be used to improve bioavailability of drug. The list of purposes for which excipients are used, as defined in international pharmacopoeias, is extremely long. Drugexcipient interaction and its importance in dosage. However, they can also give rise to inadvertent andor unintended effects such as increased degradation of the drug. 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. Drugexcipient interaction and incompatibilities sciencedirect. Physical interactions are frequently used in manufacturing of dosage form, for example to modify drug dissolution. Examples of undesirable excipientexcipient interactions are listed in table 615. Excipient interactions and best practice guide for use of excipients and types of interactions possible in different dosage forms chapters 8,1019. B interactions between drug and excipient residueimpurities department of pharmacy, adtu 10 excipients residues povidone. 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.
Such associations have important implications as food or excipientdrug interactions. Our study aimed at investigating the effects of molecular excipients present in orally administered fdaapproved drug products on the intestinal efflux transporter, bcrp abcg2, which plays a critical role in drug. Drug excipients interaction tablet pharmacy silicon. Examples of inactive ingredients include binding materials which may be excipients, dyes, preservatives, and flavoring agents. Machine learning predicts biological effects of excipients and gras compounds. If metforminassociated lactic acidosis is suspected, immediately discontinue jentadueto xr and institute general supportive measures in a hospital setting. Isothermal stress testing method is used to assess the compatibility of drugdrugdrugexcipient. Interactions of oral molecular excipients with breast cancer. Specific excipients are best suited for a particular dosage form. The calcium sulphate used as a diluent in the capsule had been replaced. This hypothesis was supported by molecular modeling studies to better understand the interactions between the.
Primary amine group of chlorpromazine undergoes maillard reaction with glycosidic hydroxyl group of reducing sugar dextrose to form imine, which finally breakdown to form amidori compounds horiuchiet al. Pdf interactions and incompatibilities of pharmaceutical. The fda approves inactive ingredients that are included in pharmaceutical products. Primary amine group of chlorpromazine undergoes maillard reaction with glycosidic hydroxyl group of reducing sugar dextrose to form imine, which finally breakdown to form amidori. Although technically inactive from a therapeutic sense, pharmaceutical excipients are critical and essential components of a modern drug product. Drug excipient interactions between 6aminocaproic acid and the excipients citric acid were found in highly concentrated solutions at ph 4.
The central role of excipients in drug formulation. Abstract in recent years there has been an increasing interest in the study of drugexcipient interactions in pharmaceutical dosage forms. The potential physical and chemical interactions between drugs and excipients can affect the chemical, physical, therapeutical properties and. Different types of chemical drug excipients interaction have been reported in the literature. This paper discusses mechanistic basis of known drugexcipient interactions with case studies and provides an overview of common underlying themes in solid, semisolid and parenteral dosage forms. Pdf drugexcipient interaction and its importance in dosage. This paper focuses on drug excipient interactions in solid dosage forms that. This article explores some of these interactions and reactions. Drug is a chemical substance obtained from either natural, synthetic or semi synthetic source, which is used for the treatment, curing, prevention or mitigation of a disease or disorder in human beings or animals. Sic is useful for proteinous drug products with excipients. These interactions adversely affect the therapeutic efficacy, safety, and appearance of the active constituent tekade et al. The evaluation of drug excipient compatibility is therefore an essential aspect of any preformulation study. Interactions and incompatibilities of pharmaceutical excipients with. A bad choice of excipient can even lead to severe intoxications, as experienced by epileptic patients in australia in the late 1960s who were taking phenytoin capsules 2.
Measure, rt retention time and compare it with non retained marker. Ethylcellulose is a freeflowing, white to light tan powder used in the pharmaceutical and food manufacturing industries. Pharmaceutical excipients in drugdrug interaction request pdf. Such associations can cause unknown drug interactions download the pdf on excipientdrug interactions here or read the article here article information. Nov 17, 2017 the resultant biological, chemical and physical properties of the drug product are directly affected by the excipient chosen, their concentration and interactions with the api. Our predictive framework can elucidate biological effects of commonly consumed chemical matter with implications on food and excipient drug interactions and functional drug formulation development. Classification of the excipients is based on their role in the pharmaceutical formulation and on their interactions influencing drug delivery, based on their chemical and physicochemical properties. A general mechanistic understanding of the basis of these interactions is essential to design robust drug products.
The potential physical and chemical interactions between drugs and excipients can affect the chemical. Excipient development for pharmaceutical, biotechnology. Three types of drugdrug interactions need to be discussed with respect to clinical situations. Excipients cannot be regarded as inert or inactive ingredients and a detailed understanding of their physiochemical properties, safety and handling, and regulatory status is essential for pharmaceutical scientists.
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