Transcript LWW PPT Slide Template Master

Dosage Form Design
Murat Kizaibek
The Need for Dosage Forms
The Need for Dosage Forms
• To provide the mechanism for the safe and convenient
delivery of accurate dosage
• To protect the drug substance from the atmosphere
• To protect the drug substance from the gastric acid (EC
tablet)
• To conceal the bitter, salty, or offensive taste or odor
• To provide liquid preparations of insoluble drugs
The Need for Dosage Forms (continued)
• To provide clear liquid dosage forms (solutions)
• To provide rate-controlled drug action
• To provide topical drug action (ointments, creams,
patches, ophthalmic, otic, nasal)
• To provide for insertion into body cavity
• To provide for placement into bloodstream
• To provide for inhalation therapy
General Considerations in
Dosage Form Design
• the nature of the illness
--normally (systemic use or oral) : tablet or capsule
--an emergency in which the patient may be comatose or
unable to take oral medication: injection
--motion sickness, nausea,and vomiting: tablets and skin
patches are used for prevention and suppositories and
injections for treatment.
• age
--infants and children younger than 5 years of age:
flavored liquid preparations
--young patient who has a productive cough or is vomiting,
gagging, or simply rebellious: injection, suppository
• anticipated condition of the patient
--patients who have difficulty in swallowing tablets whole:
chewable tablets
Design of Drug Products
• Effectiveness
• Safety
• Reliability
• Stability
– Physical
– Chemical
– Microbiological
Design of Drug Products (continued)
• Pharmaceutical elegance
– Appearance
– Organoleptic properties
• Convenience
– Ease of use
– Dosing frequency
– Consumer acceptance
Preformulation Studies
• Chemical characterization
• Physical characterization
Physical Description
• Solids, liquids, gases
• Chemical Properties
– Structure, form, reactivity
• Physical Properties
– particle size, crystalline structure, melting point, solubility
• Biological Properties
– Ability to get to site of action and elicit a response
• Herbal medicines:
–
powder of herbs or extracts, viscosity
Microscopic Examination
• Particle size
• Particle size range
• Crystal structure
• Particle shape
Heat of Vaporization
• the amount of heat required to
convert 1g of a liquid into the
vapor without a change in
temperature and is measured
in calories.
• Vapor pressure （aerosol）
• Volatile drugs can migrate
within a solid dosage form
• Personnel exposure
Melting Point
• Purity determination
• Identity
The Phase Rule
• Phase diagrams
• Phase diagrams are valuable for
interpreting interactions between
two or more components, relating
not only to melting point depression
and possible liquefaction at room
temperature but also the formation
of solid solutions, coprecipitates,
and other solid-state interactions.
Particle Size
The following characteristics of a drug substance are affected
by the particle size distribution:
• Dissolution rate
• Bioavailability
• Content uniformity
• Taste
• Texture
• Color
• Stability
• Flow characteristics
• Sedimentation rates
Polymorphism
• Crystalline form
• Amorphous form
• at least one third of all organic compounds exhibit
polymorphism.
• Melting point variation
• Solubility differences
Solubility
• Some aqueous solubility required for therapeutic efficacy
• Equilibrium solubility
• Solubility in different solvents
• Chemical modification of the drug into salt or ester forms
is frequently used to increase solubility.
Solubility and Particle Size
• Small increases in solubility can be achieved by particle
size reduction.
• Decreases in particle size may enhance dissolution rates.
Solubility and pH
• pH can affect solubility.
Dissolution
• Dissolution may be rate-limiting step in the absorption of
poorly soluble drugs.
• Can affect onset, intensity, and duration of response and
control overall bioavailability of the drug from the dosage
form
Membrane Permeability
• pKa, solubility, and dissolution rate data can provide an
indication of absorption.
pKa/Dissociation Constants
• Extent of dissociation or ionization
• Dependent on pH of medium
• Can affect absorption, distribution, and elimination
Partition Coefficient
• Octanol:water partition coefficient often used in
formulation development
Drug and Drug Product Stability
• Physical stability
• Chemical stability
• Shelf life of 2-3 years is generally desired
Drug Stability: Mechanisms of
Degradation
• Hydrolysis, solvolysis
• Oxidation
• Other processes
Drug and Drug Product Stability: Kinetics
and Shelf Life
• Chemical stability:active ingredient retains its chemical integrity
and labeled potency within the specified limits.
• Physical stability:appearance, palatability, uniformity, dissolution,
and suspendability
• Microbiological stability:microbial growth
• Therapeutic stability:The therapeutic effect remains unchanged.
• Toxicologic stability:No signifi cant increase in toxicity occurs.
Rate Reactions
• Change of drug concentration with respect to time
ZERO-ORDER RATE REACTIONS
C
t
C
FIRST-ORDER RATE REACTIONS
lnC
t
t
Q10 Method of Shelf Life Estimation
• Shelf life estimation
Reasonable estimates can often be made using the Q value of 3.
Enhancing Stability of Drug Products
• Excipients may be added to protect the drug
– Antioxidants
– Preservatives
– Chelating agents
– Buffering agents
Stability Testing
• Done at each stage of product development
• Product containers and closures must be considered
• Temperature and humidity studies
• Light studies
• Changes in physical appearance, color, odor, taste, texture
• Chemical changes of drug degradation
• Pharmacist is last professional to check for quality and
stability prior to dispensing
Herbal drugs: preformulation
• 1. processing
• 2. powder of extract or powder of plant material?
• 3. volatile?
• 4. taste or odor
• 5. solvent of extraction?
• 6. dense and hard materials
• 7.bioguided fractionation