dosage form design
DESCRIPTION
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) - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/1.jpg)
Dosage Form Design
Murat Kizaibek
![Page 2: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/2.jpg)
The Need for Dosage Forms
![Page 3: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/3.jpg)
The Need for Dosage FormsThe 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
![Page 4: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/4.jpg)
The Need for Dosage Forms (continued)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
![Page 5: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/5.jpg)
General Considerations in
Dosage Form Design
![Page 6: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/6.jpg)
• 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.
![Page 7: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/7.jpg)
• 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
![Page 8: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/8.jpg)
Design of Drug ProductsDesign of Drug Products
• Effectiveness
• Safety
• Reliability
• Stability
– Physical
– Chemical
– Microbiological
![Page 9: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/9.jpg)
Design of Drug Products (continued)Design of Drug Products (continued)
• Pharmaceutical elegance
– Appearance
– Organoleptic properties
• Convenience
– Ease of use
– Dosing frequency
– Consumer acceptance
![Page 10: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/10.jpg)
Preformulation StudiesPreformulation Studies
• Chemical characterization
• Physical characterization
![Page 11: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/11.jpg)
Physical DescriptionPhysical 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
![Page 12: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/12.jpg)
Microscopic ExaminationMicroscopic Examination
• Particle size
• Particle size range
• Crystal structure
• Particle shape
![Page 13: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/13.jpg)
Heat of VaporizationHeat 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
![Page 14: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/14.jpg)
Melting PointMelting Point
• Purity determination
• Identity
![Page 15: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/15.jpg)
The Phase RuleThe 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.
![Page 16: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/16.jpg)
Particle SizeParticle Size
• Dissolution rate
• Bioavailability
• Content uniformity
• Taste
• Texture
• Color
• Stability
• Flow characteristics
• Sedimentation rates
The following characteristics of a drug substance are affected by the particle size distribution:
![Page 17: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/17.jpg)
PolymorphismPolymorphism
• Crystalline form
• Amorphous form
• at least one third of all organic compounds exhibit polymorphism.
• Melting point variation
• Solubility differences
![Page 18: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/18.jpg)
SolubilitySolubility
• 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.
![Page 19: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/19.jpg)
Solubility and Particle SizeSolubility and Particle Size
• Small increases in solubility can be achieved by particle size reduction.
• Decreases in particle size may enhance dissolution rates.
![Page 20: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/20.jpg)
Solubility and pHSolubility and pH
• pH can affect solubility.
![Page 21: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/21.jpg)
DissolutionDissolution
• 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
![Page 22: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/22.jpg)
Membrane PermeabilityMembrane Permeability
• pKa, solubility, and dissolution rate data can provide an indication of absorption.
![Page 23: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/23.jpg)
pKa/Dissociation ConstantspKa/Dissociation Constants
• Extent of dissociation or ionization
• Dependent on pH of medium
• Can affect absorption, distribution, and elimination
![Page 24: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/24.jpg)
Partition CoefficientPartition Coefficient
• Octanol:water partition coefficient often used in
formulation development
![Page 25: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/25.jpg)
Drug and Drug Product StabilityDrug and Drug Product Stability
• Physical stability
• Chemical stability
• Shelf life of 2-3 years is generally desired
![Page 26: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/26.jpg)
Drug Stability: Mechanisms of DegradationDrug Stability: Mechanisms of Degradation
• Hydrolysis, solvolysis
• Oxidation
• Other processes
![Page 27: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/27.jpg)
Drug and Drug Product Stability: Kinetics and Shelf LifeDrug 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.
![Page 28: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/28.jpg)
Rate ReactionsRate Reactions
• Change of drug concentration with respect to time
![Page 29: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/29.jpg)
ZERO-ORDER RATE REACTIONS
FIRST-ORDER RATE REACTIONS
C
t
lnC
t
C
t
![Page 30: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/30.jpg)
Q10 Method of Shelf Life EstimationQ10 Method of Shelf Life Estimation
• Shelf life estimation
Reasonable estimates can often be made using the Q value of 3.
![Page 31: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/31.jpg)
Enhancing Stability of Drug ProductsEnhancing Stability of Drug Products
• Excipients may be added to protect the drug
– Antioxidants
– Preservatives
– Chelating agents
– Buffering agents
![Page 32: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/32.jpg)
Stability TestingStability 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
![Page 33: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/33.jpg)
Herbal drugs: preformulation
![Page 34: Dosage Form Design](https://reader035.vdocuments.us/reader035/viewer/2022062408/56813ae1550346895da33136/html5/thumbnails/34.jpg)
• 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