Stability Testing Of Drugs And Pharmaceuticals Pdf
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- A REVIEW ON STABILITY TESTING GUIDELINES OF PHARMACEUTICAL PRODUCTS
- Photostability and Photostabilization of Drugs and Drug Products
- Regulatory Guidelines on Stability Testing and Trending of Requirements
Photostability studies of drugs and drug products are an integral part of the product development process in the pharmaceutical industry. These studies are carried out to ensure quality, efficacy, and safety of the formulated products during manufacture, storage, and use. This review deals with the concept of photostability and related aspects and the literature available in the field. It highlights the role of the photochemistry in the photostability studies, describes the functional groups important for the photoreactivity of drugs, explains photophysical processes, and deals with the kinetics of photochemical reactions.
A REVIEW ON STABILITY TESTING GUIDELINES OF PHARMACEUTICAL PRODUCTS
Quality consistencies of drug products are essential to guarantee expected therapeutic activities, and achieving consistent qualities for herbal products is challenging because of their physicochemical complexities and inherent variabilities. Regulatory authorities worldwide have issued regulations or guidelines for stability testing parameters and testing procedures for herbal products stored in proposed conditions.
Physical, chemical, and biological stability tests were compared between different dosage forms, and the testing conditions temperature and relative humidity used for long-term, accelerated, or intermediate testing were included in the guidelines and regulations.
Comparisons of global regulations and guidelines addressing stability testing are fundamental for the international harmonization of herbal product quality assessments. This review aids understanding of the global situation regarding the testing of herbal product quality with respect to storages. The maintenance of herbal product quality during storage is critical for guaranteeing therapeutic activity. Stability testing is used to evaluate how herbal products retain their properties under specified storage conditions stressed by heat, moisture, light, oxygen, various physical and chemical conditions e.
Herbal products are produced in various dosage forms e. The stabilities of finished herbal products can be determined by testing for properties susceptible to storage conditions and include physical organoleptic characteristics, physical condition, particle size, etc. These properties can all affect the qualities, safeties, or the efficacies of herbal products, and thus, the shelf lives of herbal products should be determined by stability testing [ 3 ]. Furthermore, different stability protocols are used in different countries as herbal products are generally developed to meet national regulations.
Global harmonization of stability testing has been recently emphasized in the context of herbal drug development, but the adoption of international standards can only be achieved by sharing national experiences and information [ 4 ].
We searched guidelines and regulations from global authorities and countries where the stability testing is required for quality maintenance of herbal products or final herbal preparations. Testing parameters or quality testing indicators were crucially provided according to different dosage forms of herbal products.
Conditions for long-term, accelerated, and intermediate testing e. Guidelines and regulations which requires quality of only chemical drugs were excluded. ASEAN issues the stability testing guidelines to ensure quality maintenance of final herbal products traditional medicines in specified packages that apply to recommended storage conditions and times. These guidelines require that physical, chemical, and microbiological parameters of finished products should be addressed.
The EEC requires storage stability studies to be conducted in herbal medicinal preparations for registration in accordance with regulations for pharmaceutical substances and medicinal products [ 6 ]. Stability testing involves determining values of physical, chemical, biological, microbiological indicators, preservative contents e.
The regulations require that all medicinal products should be evaluated in terms of appearance, active ingredient, degradation products, preservative, and antioxidant contents. Asterisks indicate optional test parameters. According to the EMA guidelines, all herbal medicinal products should be tested for the compliance with specifications including descriptions, identifications, assay, impurities, and microbial limits. The following testing parameters are also specified: tablets coated and uncoated and hard capsules dissolution, disintegration, hardness, friability, uniformity of mass, water content, and microbial limits ; oral suspension uniformity of mass, pH, microbial limits, antimicrobial preservative content, antioxidant preservative content, extractables, alcohol content, dissolution for oral suspensions , and resuspension for dry powder products , particle-size distribution, redispersibility, rheological properties for relatively viscous solutions or suspensions, viscosity, specific gravity for oral suspensions, relatively viscous, or nonaqueous solutions , reconstitution time, and water content ; and herbal teas loss on drying, identification, purity, uniformity of mass or average mass of the sachet, assay, particle size, and microbial quality or microbial limit testing [ 8 , 9 ].
ICH guidelines provide general requirements for the storage stability testing of new drug products that cover chemical substances with respect to description, identification, assay, and impurity contents [ 10 ]. The WHO expert committee publishes technical reports annually on specifications for pharmaceutical preparations and guidelines on good herbal processing practices for herbal medicines Annex 1 and on stability testing for active pharmaceutical ingredients and finished pharmaceutical products Annex 10 [ 3 ].
General requirements of the stabilities of finished pharmaceutical products include appearance, assay, and degradation products and preservative and antioxidant content. Specific parameters are also provided according to dosage forms of the product, that is, as liquids, solids, or others [ 3 ]. Liquid herbal dosage forms include fluid extracts, decoctions, infusions, tinctures, syrups, and oral solutions, which are tested for precipitate formation, clarity, pH, viscosity, extractables, and microbial contamination level.
Oral suspensions are tested for precipitate formation, clarity, pH, viscosity, extractables, microbial contamination level, dispersibility, rheological properties, mean size or distribution of particles, and polymorphic conversion. Oral emulsions are tested for precipitate formation, clarity, pH, viscosity, extractables, microbial contamination level, phase separation, and globule mean size or distribution.
For aromatic water, and powders or granules for oral solutions or suspensions, water content and reconstitution time are tested [ 3 ]. Solid herbal dosage forms include herbal tea bags, plant powders, dry extract powders, granules, pills, hard gelatin capsules, soft gelatin capsules, tablets, and lozenges. Hard gelatin capsules are tested for brittleness, dissolution, disintegration, water content, and microbial contamination level. Soft gelatin capsules are tested for dissolution, disintegration, microbial contamination level, pH, leakage, and pellicle formation.
Tablets are tested for dissolution, disintegration, water content, hardness, and friability [ 3 ]. Other dosage forms include ointments, creams, and salves which are tested for clarity, homogeneity, pH, suspendability for lotions , consistency, viscosity, particle-size distribution for suspensions , microbial contamination level, sterility, and weight loss.
Ophthalmic and otic products e. Inhalers are tested for dose content uniformity, labelled number of medication actuations per container that meet stated dose delivery, aerodynamic particle-size distribution, microscopic evaluation, water content, leak rate, level of microbial contamination, valve delivery or shot weight, extractables or leachables from plastic and elastomeric components, weight loss, pump delivery, foreign particulate matter, extractables or leachables from plastic, and elastomeric components of the container, closure, and pump.
Plasters and patches are tested for in vitro release rates, leakage, level of microbial contamination, sterility, peel strength, and adhesive forces. Medicated oils are also included in other dosage forms, but testing parameters are not provided [ 3 ]. The Australian government provides mandatory guidelines for the stability testing of complementary medicines in different dosage forms as follows: solutions, suspensions, creams, ointments, tablets produced by direct compression , tablets produced by granulation , capsules two-piece, produced by dry mixing , capsules two pieces, produced by granulation , soft capsules soft gels containing solutions, soft capsules soft gels containing suspensions, and powder mixes [ 11 ].
The Brazilian Health Regulatory Agency ANVISA adopts the position that stabilities herbal products depending on environmental factors temperature, humidity, and light as well as product-related parameters physical and chemical properties of active substances and excipients, pharmaceutical form, product composition, manufacture, and properties of packaging materials.
Stability studies should be of an accelerated nature and were conducted long term to establish shelf-life and suitable storage conditions [ 13 ]. In addition, microbial testing is required for all dosage forms [ 14 ]. Canadian government requires storage stability testing for natural and nonprescription health products to determine shelf lives after packing and storage conditions. These tests address purity, physical characteristics, level of medicinal ingredients quantity per dosage unit, and potency [ 15 ].
Canadian government prescribes guidelines that provide physical testing parameters for different dosage forms, as follows: tablets, caplets, and capsules for immediate release description, disintegration, and weight variation or average weight ; rapidly dissolving tablets description, dissolution, and weight variation or average weight ; tablets and capsules for extended release, combined release, or timed release description, dissolution, weight variation or average weight, and uniformity of dosage unit ; tablets and capsules for delayed release, including enteric coated tablets and capsules description, disintegration, and weight variation or average weight ; oral solutions and suspensions description and preservative efficacy ; topical preparations description and preservative efficacy ; transdermal patches description, uniformity of dosage unit, and adhesive strength or peel force ; and metered dosage forms number of discharges per container and delivered dose uniformity [ 16 ].
The Chinese government requires accelerated and long-term stability testing to provide shelf lives of herbal products and appropriate storage conditions [ 17 ]. Egyptian Drug Authority requires that finished products satisfy minimum specifications for registration, and these include the following: 1 common quality parameters: physical appearance color, odor, form, shape, size, and texture , water content, identity tests, or qualitative determination of relevant substances of the plants e.
Description, identification except for medicinal membrane , assay, and microbial limits injected medications, plasters, and adhesive plaster are excluded are generally required in all dosage forms [ 20 ]. Asterisks indicate optional test parameters [ 22 ]. The Pharmaceutical Safety and Environmental Health Bureau Ministry of Health, Labor and Welfare provides quality parameters for Kampo dosage forms, as follows: powders content, description, identification, loss on drying, uniformity, and assay ; granules content, description, identification, loss on drying, uniformity, disintegration, and assay ; uncoated and film-coated tablets content, description, identification, loss on drying, uniformity, disintegration, and assay ; sugar-coated tablets content, description, identification, loss on drying, uniformity, and assay ; and hard and soft capsules content, description, identification, loss on drying, uniformity, disintegration, and assay [ 23 ].
It should be noted that stability testing procedures should be conducted in accordance with ICH guidelines [ 24 ]. Kenyan government demands a minimum range of specifications be met by finished products according to guidelines for the registration of herbal and complementary products. General specifications include tests for microbiological contamination and toxins, physical appearance color, odor, form, shape, size, and texture , water content, identity tests, qualitative determination, quantification of relevant active ingredients, and tests for residual solvents.
The guideline prescribes that the physical and chemical stabilities after long-term storage period should comply with ICH guidelines [ 25 ]. The Ministry of Food and Drug Safety MFDS requires the results of stability tests conducted in accordance with existing regulations, which provide long-term, accelerated, and intermediate testing for prescribed times under specified storage conditions, for the registration of herbal products [ 26 , 27 ].
The Food and Drug Bureau of the Philippines requires that stability studies be conducted under recommended conditions and should determine the most appropriate conditions for storage and shelf life. The government also requires physical descriptions, tests, and quality standards of finished products herbal medicines and traditionally used herbal products including organoleptic and macroscopic descriptions appearance, texture, color, odor, and taste , moisture content, pH, alcohol content if applicable , microbial limits, and identification.
In addition, the Philippines government provides specific parameters of specifications for different dosage forms such as tablets weight variation, content uniformity, disintegration, hardness test, friability, and microbial testing ; capsules weight variation, content uniformity, and microbial testing ; syrups and liquids viscosity, pH, and microbial testing ; suspensions suspendability, homogeneity, viscosity, minimum fill, pH, and microbial testing ; ointments, creams, and semisolid preparations palpability, homogeneity, pH, melting point, allergenicity, and microbial testing ; suppositories and pessaries allergenicity and microbial testing ; and decoctions, infusions, extracts liquids, pillulars, and powders , tinctures, syrups, lotions, and emulsions must pass all requirements specified in Pharmacopoeias of other countries [ 28 , 29 ].
The Qatar government provides general requirements for the quality specifications of herbal and dietary supplement products for registration.
These include physical examination, identification chemical, spectroscopic, or chromatographic tests , main ingredient levels, heavy metals concentrations, microbial limits, and other quality standards according to dosage form, which include disintegration, dissolution, friability, hardness, water, pH, water content, ash, and residue on ignition tests. Applicable dosage forms are tablets, hard, and soft gelatin capsules, semisolid preparations ointments, creams, and gels , herbal tea bags and sachets, syrups, oral suspensions, oral drops, or powders.
General requirements of quality parameters for sterile products eye drops, contact lenses, and dermal fillers additionally include pH, osmolarity, viscosity, volume, and bacterial endotoxin test for dermal filler products [ 30 ]. The Switzerland agency recommends that bulk and finished medicinal products in the form of capsules or tablets containing herbal preparations or granules require drug formulation-specific testing parameters e. Stability tests are required to be conducted in accordance with international ICH guidelines, which include testing parameters such as description, identity, loss on drying, assay, and microbial purity [ 31 ].
The Food and Drug Administration FDA requires that the stability of botanical drug substance and drug products be monitored using stability-related analytical methods or biological assay [ 32 ] and presents the quality testing attributes required for the registration of botanical drug products to ensure that clinical protocols are properly designed during phases 1, 2, and 3 clinical studies. General attributes include appearance, chemical identification, assay for active constituents or characteristic markers, biological assay optional , strength by dry weight of drug substance , and microbial limits and specific attributes of dosage forms dissolution for solid oral products, sterility, nonpyrogenicity, and animal safety testing for parenterals [ 33 ].
The Zambian government requires specifications and test methods of final products in all dosage forms comply with their guideline for the registration of herbal medicines, which includes description, identity, assay, and impurities degradation product of active raw materials and microbial limits.
Additional tests for specific dosage forms are also provided by the guideline, as follows: gelatin capsules and coated and uncoated tablets dissolution, disintegration, hardness, friability, uniformity of dosage units, and water content ; oral liquids uniformity of contents, pH, microbial limits, antimicrobial and antioxidant preservative content, extractable from the container or closure system, alcohol content, dissolution for suspensions and powders for suspension, redispensability for suspensions, viscosity for suspensions or viscous solutions, specific gravity for suspensions or viscous solutions, and water content for powders for reconstitution [ 34 ].
Considering global regulations and guidelines, testing parameters of oral or external dosage forms, which are commonly specified in more than two global guidelines, are classified into three groups: 1 physical parameters, e. Global regulations for the stability testing of finished herbal products under long-term, accelerated, and intermediated conditions require that the frequency of stability studies be sufficient to establish a product's stability profile throughout its proposed shelf-life, especially for long-term stability testing.
Herbal products should be evaluated in terms of thermal stability or moisture susceptibility based on consideration of durations of storage, transportation, and use.
Moreover, the effects of storage temperature and moisture relative humidity should be adequately considered as they are the most influential factors for quality of herbal products.
Herbal products are packed in either general, semipermeable allows solvent or moisture migration through the container surface , or impermeable containers, which influence the effects of storage temperature and relative humidity [ 3 , 7 , 35 , 36 ].
Enayatifard et al. Kim et al. Pushpalatha et al. Sawant et al. Alexander et al. Huang et al. Efforts by global authorities and countries to improve the qualities of herbal products continue to increase.
However, the different regulations adopted inhibit the scopes of studies and harmonization of quality assessments of herbal products. In the present study, we provide stability testing parameters and methods and an overview of the guidelines and regulations of 5 global authorities and 15 countries. We hope that the information provided further understanding and collaborative studies on the stability testing of herbal products in their various dosage forms.
National Center for Biotechnology Information , U. Evid Based Complement Alternat Med. Published online Oct Author information Article notes Copyright and License information Disclaimer. Jung-Hoon Kim: rk. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Quality consistencies of drug products are essential to guarantee expected therapeutic activities, and achieving consistent qualities for herbal products is challenging because of their physicochemical complexities and inherent variabilities. Introduction The maintenance of herbal product quality during storage is critical for guaranteeing therapeutic activity.
An Overview of Stability Testing of Herbal Dosage Forms We searched guidelines and regulations from global authorities and countries where the stability testing is required for quality maintenance of herbal products or final herbal preparations. Stability Testing Parameters 2. ASEAN ASEAN issues the stability testing guidelines to ensure quality maintenance of final herbal products traditional medicines in specified packages that apply to recommended storage conditions and times.
The EEC The EEC requires storage stability studies to be conducted in herbal medicinal preparations for registration in accordance with regulations for pharmaceutical substances and medicinal products [ 6 ].
ICH ICH guidelines provide general requirements for the storage stability testing of new drug products that cover chemical substances with respect to description, identification, assay, and impurity contents [ 10 ].
Photostability and Photostabilization of Drugs and Drug Products
Stability of a pharmaceutical product means how long it can maintain its original form without any visible changes under the influence of various environmental factors like temperature, humidity, light. Stability testing is the statistical analysis of how long a pharmaceutical product can be stored without any change in its original chemical composition. Pharmaceutical products when stored for long durations tend to undergo changes and release byproducts. Stability testing provides evidence on how certain pharmaceutical drugs can be stored at room temperature and in controlled conditions. The physical, chemical and microbial properties of a pharmaceutical product may change under extreme storage conditions.
Stability testing is required to demonstrate that a pharmaceutical product meets its acceptance criteria throughout its shelf life and to gain regulatory approval for commercialization. Assessing drug product stability and safety can be quite complicated, and stability profile can impact many functional areas, including analytical testing, formulation development, toxicology, quality, and regulatory affairs. Handbook of Stability Testing in Pharmaceutical Development: Regulations, Methodologies, and Best Practices is the first volume to cover all aspects of stability testing in pharmaceutical development. It presents a scientific understanding of regulations and balances methodologies and best practices. Comprising 17 chapters, it provides a wealth of resources for pharmaceutical companies, educational institutions, and manufacturing laboratories to use as either a supplementary text for stability training courses or as a reference book for pharmaceutical practitioners. This collective work was written by a group of prominent international experts, who have been directly responsible for instituting industry best practices and establishing the current stability guidelines.
Enabling you to identify and mitigate the intrinsic risk in your operations, supply chains and business processes. Learn More. Evaluating how your products and services meet and exceed quality, safety, sustainability and performance standards. Validating the specifications, value and safety of your raw materials, products and assets. Formally confirming that your products and services meet all trusted external and internal standards.
The stability test assesses how the quality of a drug substance or a drug product changes with time under the influence of various factors such as temperature.
Regulatory Guidelines on Stability Testing and Trending of Requirements
Quality consistencies of drug products are essential to guarantee expected therapeutic activities, and achieving consistent qualities for herbal products is challenging because of their physicochemical complexities and inherent variabilities. Regulatory authorities worldwide have issued regulations or guidelines for stability testing parameters and testing procedures for herbal products stored in proposed conditions. Physical, chemical, and biological stability tests were compared between different dosage forms, and the testing conditions temperature and relative humidity used for long-term, accelerated, or intermediate testing were included in the guidelines and regulations. Comparisons of global regulations and guidelines addressing stability testing are fundamental for the international harmonization of herbal product quality assessments. This review aids understanding of the global situation regarding the testing of herbal product quality with respect to storages.
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