midterm 1 Flashcards
It importance has been recognized in the pharmaceutical industry.
QUALITY SYSTEMS
It is evident that it is a valuable component of an effective quality system.
QUALITY RISK MANAGEMENT
It is defined as the combination of the probability of occurrence of HARM and the SEVERITY of that harm.
RISK
It is assured based on appropriate risk based DECISION-MAKING throughout the PRODUCT LIFECYCLE, such that the attributes that are important to the quality of the drug (medicinal) product are maintained and the product remains safe and effective.
PRODUCT QUALITY
50-200 healthy subjects (usually) or patients who are not expected to benefit from the IMP
PHASE 1 CLINICAL TRIAL
100-400 patients with the target disease
PHASE 2 CLINICAL TRIAL
1000-5000 patients with the target disease
PHASE 3 CLINICAL TRIAL
Many thousands or millions of patients with the target disease
PHASE 4 CLINICAL TRIAL
It is a systematic process for the assessment, control, communication and review of risks to the quality of the drug (medicinal) product across the product lifecycle.
QUALITY RISK MANAGEMENT
Zone I
TEMPERATE ZONE
Zone II
MEDITERRANEAN/SUBTROPICAL ZONE
Zone III
HOT DRY ZONE
Zone IVa
HOT HUMID/TROPICAL ZONE
Zone IVb
HOT/HIGHER HUMIDITY
It can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used.
STRESS TESTING OF DRUG SUBSTANCE
It will depend on the individual drug substance and the type of drug product involved.
NATURE OF STRESS TESTING
It is likely to be carried out on a single batch of the drug substance.
STRESS TESTING
It should be an integral part of stress testing.
PHOTOSTABILITY TESTING
Data from formal stability studies should be provided on at least _______ of the drug substance.
THREE PRIMARY BATCHES
The stability testing should cover, as appropriate, the ____, ____, ____, _____ attributes.
PHYSICAL
CHEMICAL
BIOLOGICAL
MICROBIOLOGICAL
____ for a drug substance is defined as failure to meet its specification.
SIGNIFICANT CHANGE
It involves a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture.
ICH STABILITY STUDIES
The long-term testing should be performed over a minimum of ___
12 MONTHS
It is an essential operation in the production of drugs.
It is a procedure or set of procedures designed to ensure the output of uniform batches of drugs conforms to the established specifications.
QUALITY CONTROL OF PHARMACEUTICAL FORMULATIONS
Different types of dosage forms
SOLID DOSAGE FORM
LIQUID DOSAGE FORM
SEMI-SOLID DOSAGE FORM
GAS DOSAGE FORM
It means a physical form by which drug molecules are delivered into the site of action.
DOSAGE FORMS
These are the most commonly used dosage form because of the stability and ease of mass production.
SOLID DOSAGE FORMS
EXAMPLES OF SOLID DOSAGE FORMS
TABLETS
CAPSULES
GRANULES
SACHETS
POWDER
DRY POWDER INHALERS
CHEWABLE
Advantages of Solid Dosage Forms
• More stable than other dosage forms.
• Easy to handle.
• More accurate of the dosage form.
• No preservation required.
Disadvantages of Solid Dosage Forms
• Expensive Machines.
• Tough to swallow for kids and patients in sleeping condition.
Unit Dose Solid Dosage Forms
• Tablets
• Capsules
• Granules
• Sachets
• Lozenges
• Pills
• Dry powder inhaler
• Chewables
Bulk Dose Solid Dosage Forms
POWDER (External and Internal)
These are compressed solid dosage form contain therapeutic active ingredients and excipients.
TABLETS
These are solid dosage forms where the therapeutic active ingredient granules are enclosed within a hard or soft soluble shell.
CAPSULES
These are solid dosage forms made up of agglomeration of smaller particles of powders.
GRANULES
These are solid dosage forms containing therapeutic ingredients. Small size spherical granules packed into a small bag or pouch packet.
SACHETS
These are the solid dosage form that dissolves slowly into the mouth. It contains a drug along with flavoring and sweetening agents.
LOZENGES
It refers to those materials which are used in every dosage form. But it doesn’t have any therapeutic effects or side effects.
EXCIPIENTS
Its role is to make the plasticity in the tablet formulation.
It helps to maintain the inter-particle bonding strength and to achieve mechanical strength and sometimes for the drug release properties.
BINDING AGENTS
Natural Polymers (Binding Agents)
STARCH
GELATIN
ACACIA
TRAGACANTH
Synthetic Polymer (Binding Agents)
HYDROXYPROPYLMETHYLCELLULOSE
METHYL CELLULOSE
ETHYL CELLULOSE
POLYETHYLENE GLYCOL
Sugar (Binding Agents)
GLUCOSE
SUCROSE
SORBITOL
This is used in tablet preparation. Its is protecting the drug from environmental moisture, light, or the acidic environment of the stomach and it also masks the bitter taste of many drugs.
COATING AGENTS
Types(?) of Coating Agents
SUGAR COATING
FILM COATING
ENTERIC COATING
These are basically used to protect the formulation from the attack of microorganisms. Such as bacterial growth, fungus growth, etc.
PRESERVATIVES
Examples of Preservatives
PHENOL
PARABENS
ARYL AND ALKYL ACIDS
These are used to giving an attractive outlook for the patients.
COLORING AGENTS
Example of Natural Colors
TURMERIC
TITANIUM DIOXIDE
Example of Synthetic Colors
ERYTHROSINE
TARTRAZINE
These are used in basically chewable tablets. To cover up the unpleasant taste of the tablet or any pharmaceutical formulation.
SWEETENING AGENTS
Examples of Sweetening Agents
SUCROSE
FRUCTOSE
Semisolids constitute a significant proportion of pharmaceutical dosage forms. They serve as carriers for drugs that are topically delivered by way of the skin, cornea, rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane, and external ear lining.
SEMISOLID DOSAGE FORMS
They are normally presented in the form of creams, gels, ointments, or pastes. They contain one or more active ingredients dissolved or uniformly dispersed in a suitable base and any suitable excipients such as emulsifiers, viscosity increasing agents, anti microbial agents, antioxidants’, or stabilizing agents.
TOPICAL SEMISOLID DOSAGE FORMS
It contains very limited quantities of a liquid or aqueous phase.
SEMISOLID DOSAGE FORMS
Surface pH can be measured by using a:
SIMPLE PH METER
PROBE-TYPE PH METER
If the formulation is thick, the pH can be measured by
DILUTING IT WITH DISTILLED WATER
These are plastic in behavior hence they retain their shape on application of outside force.
SEMISOLID DOSAGE FORMS
Two Phases of Semisolid Dosage Forms
CONTINUOUS PHASE (EXTERNAL)
DISPERSED PHASE (INTERNAL)
Examples of Continuous (External) Phase
SUPPOSITORIES
PESSARIES
Examples of Dispersed (Internal) Phase
CREAM
OINTMENT
PASTE
The physical properties of the dosage form depend upon various factors:
- SIZE OF THE DISPERSED PARTICLES
- INTERFACIAL TENSION BETWEEN PHASES
- PARTITION COEFFICIENT OF THE ACTIVE INGREDIENT BETWEEN THE PHASES AND PRODUCT RHEOLOGY
Advantage of semi-solid dosage form:
• It is used externally
• Probability of side effect can be reduce
• Local action
• First pass gut and hepatic metabolism is avoided.
• Patient compliance is increased, the drug termination is problematic cases is facilitated as compared with other routes of drug administration.
Disadvantages of semi-solid dosage form:
• There is no dosage accuracy in this type of dosage form
• The base which is used in the semi-solid dosage form can be easily oxidized.
• If we go out after using semi-solid dosage form problems can occur.
These are homogenous, semi-solid preparations intended for external application to the skin or mucous membrane.
They are used as emollients or for the application of active ingredients to the skin for protective, therapeutic, or prophylactic purpose and
where a degree of occlusion is desired.
OINTMENTS
These are semisolid preparations for external application to skin or mucous membranes. Their composition softens but does not melt upon application to the skin.
- Therapeutically, it functions as skin protectives and emollients, but they are used primarily as vehicles for the topical application of drug substances.
OINTMENTS
Types of Ointments
HYDROPHOBIC OINTMENT
WATER-EMULSIFYING OINTMENT
HYDROPHILIC OINTMENT
These are usually anhydrous and can absorb only small amounts of water.
Typical bases used for their formulation are water-insoluble hydrocarbons such as hard, soft and liquid paraffin, vegetable oil, animal fats, waxes, synthetic glycerides and polyalkyl siloxanes.
HYDROPHOBIC (LIPOPHILIC) OINTMENTS
It can absorb large amounts of water.
They typically consist of a hydrophobic fatty base in which a w/o agent, such as wool fat, wool alcohols, sorbitan esters, mono glycerides, or fatty alcohols can be incorporated to render them hydrophilic.
WATER-EMULSIFYING OINTMENT
They may also be w/o emulsions that allow additional quantities of aqueous solutions to be incorporated. Such ointments are used especially when formulating aqueous liquids or solutions.
WATER-EMULSIFYING OINTMENT
Its bases are miscible with water. The bases are usually mixture of liquid and solid polyethylene glycols (macrogols).
HYDROPHILIC OINTMENT
These are homogeneous, semi-solid preparations consisting of opaque emulsion systems.
Their consistency and rheological properties depend on the type of emulsion, either water-in-oil (w/o) or oil-in –water (o/w), and on the nature of the solids in the internal phase.
CREAMS
They are intended for the application to the skin or certain mucous membranes for protective, therapeutic, or prophylactic purposes, especially where an occlusive effect is not necessary.
CREAMS
These are semisolid dosage forms that contain one or more drug substances dissolved or dispersed in a suitable base, usually oil in- water emulsion or aqueous microcrystalline dispersion of long-chain fatty acids or alcohols that are water washable and are cosmetically and aesthetically acceptable.
CREAMS
These are usually homogeneous, clear, semi-solid preparation consisting of a liquid phase within a three-dimensional polymeric matrix with physical or sometimes chemical cross linkage by means of suitable gelling agents.
GELS
These are semisolid systems that consist of either suspensions of small inorganic particles or large organic molecules interpenetrated by a liquid.
GELS
Its bases usually consist of liquid paraffin with polyethylene or fatty oils gelled with colloidal silica or aluminium or zinc soaps.
HYDROPHOBIC GEL (OLEOGEL)
Its bases usually consist of water, glycerol, or propylene glycol gelled with suitable agents such as tragacanth, starch, cellulose derivatives, carboxyvinyl polymers, and magnesium aluminium silicates.
HYDROPHILIC GEL (HYDROGEL)
These are homogeneous, semi-solid preparations containing high concentrations of insoluble powdered substances (usually not less than 20%) dispersed in a suitable base.
PASTES
These are usually less greasy, more absorptive, and stiffer in consistency than ointments because of the large quantity of powdered ingredients present. Some pastes consist of a single phase, such as hydrated pectin, and others consist of a thick, rigid material that does not flow at body temperature.
PASTES
These are semisolid dosage forms that contain one or more drug substances incorporated in a base with large proportions of finely dispersed solids.
PASTES
It is an ancient form of topical medication also known as a cataplasma.
It is a soft mass of vegetable constituents or clay, usually heated before application.
POULTICES
It is prepared by mixing and heating dried, heavy kaolin and boric acid with glycerine.
KAOLIN POULTICE BP
Its purpose is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the drug substance or a shelf life for the drug product and recommended storage conditions.
STABILITY TESTING
It is different in all the countries in the world. Stability studies of the pharmaceutical drug should be done according to the climatic conditions of the country.
CLIMATE
Risk Assessment
HAZARD IDENTIFICATION
RISK ANALYSIS
RISK EVALUATION
RISK CONTROL
RISK REDUCTION
RISK ACCEPTANCE
RISK REVIEW
REVIEW EVENTS
Initiate Quality Risk Management Process
Risk Assessment
Risk Control
Output/Result of the Quality Risk Management Process
Risk Review
It should also evaluate the susceptibility of the drug substance to hydrolysis across a wide range of pH values when in solution or suspension.
STRES TESTING
The stability studies should be conducted on the drug substance packaged in a container closure system that is the same as or simulates the packaging proposed for storage and distribution.
CONTAINER CLOSURE SYSTEM
It should include testing of those attributes of the drug substance that are susceptible to change during storage and are likely to influence quality, safety, and/or efficacy.
STABILITY STUDIES
Intermediate minimum time period and storage condition
6 months (30 degrees C)
Accelerated minimum time period and storage condition
6 months (40 degrees C)
Long term minimum time period and storage condition
12 months (25 degrees or 30 degrees C)
It includes situations where product availability may be impacted, leading to potential patient harm.
RISK TO QUALITY
