FORMULASI DAN EVALUASI SEDIAAN
FARMASI
PSPA 35 FFS-UHAMKA 2021
Pharmaceutical Formulation
◦ The objective of drug formulation
◦ Factors considered during pharmaceutical formulation
•
Physical, chemical, and mechanical properties of drug substances
•
Polymofphism, solubility, pH, particle size of drug
•
In-active ingredients or excipients to be added
•
Effectiveness of the drug in phase I clinical-trials
•
Result of drug stability studies
◦ Type of formulation
➢Enteral >> solid, liquid → oral
➢Parenteral >> liquid → intravascular
➢Topical >> solid, semisolid, liquid, aerosol →skin application
◦ Container/Packaging
Formulator/Formulation Scientist :
• Pre-formulation studies
✓Analyze the result
• Formulation development
• Evaluation the final product
PHARMACEUTICAL DOSAGE FORMS
SOLID DOSAGE FORMS
• Tablets
• Effervescent tablets
• Buccal tablets
• Orally desintegrating tablets
• Sustained controlled release
• Capsules
• Granules
• Powder
SEMI SOLID DOSAGE FORMS
• Ointments
• Creams
• Gel
NOVEL DRUG DELIVERY SYSTEM
NON-STERIL
◦ Syrups
◦ Elixirs
◦ Supensions
◦ Emulsions
STERIL
◦ Parenterals
◦ Eye drop
AEROSOLS NASAL SPRAY COSMETICS
LIQUID DOSAGE FORMS
• Monitor product quality
• Quantitative evaluation
• Check chemical breakdown
• Check interactions between physical components
evaluation
Evaluations of tablets
◦ General appearance
◦ Weight variation
◦ Content uniformity
◦ Mechanical strength
Friability
Hardness
✓ Oral tablets: 4-10 kg hardness
✓ Chewable tablets: 3 kg (softer)
✓ Sustained release tablets:
10-20 kg (much harder)
◦ Tensile strength
◦ Disintegration
◦ Dissolution
Bioavailability of drugs
Two objectives in development of In-vitro
dissolution test Rate of dissolution proportional
to :
- efficacy of product - bioavailability
Evaluation of effervescent tablets
◦ Effervescent time
◦ Water content and moisture uptake studies
◦ → humidity conditions, RH
◦ → check by Karl Fisher method
3 tablets were exposed to three different humidity
condition (23°C) → controlled by humidity chambers ( 31%. 45%.
73% RH) →constructed using various saturated salt solutions (in desiccator)
Evaluation of Buccal tablets
Parameters:
◦ Residence time :
◦ In vitro
◦ In-vivo
Using dissolution tes (USP); 800 mLisotonic
Buffer PO4
Evaluations of orally disintegrating tablets (ODT)
ODT →
Parameters:
◦ Wetting time
◦ Disintegration time
◦ → less than one minute and actual dis.time that patient can experience ranges from 5-30 seconds
Evaluations of capsules
◦ Stability test
✓ Shell integrity test → performed of integrity of capsule sheel
✓ Determination of shelf life → expire date of packaged capsules (unde normal storage conditions)
oInvariability test
✓Weight variation
✓Content uniformity oDisintegration test
◦
Dissolution test; using dissolution apparatus:
✓Rotating basket
✓Rotating paddle
◦
Moisture permeation test
→
to assure the suitability of containers for packaging of capsules
Evaluation of granules
◦ Flow properties → 1. Frictional force
2. Surface tension force
3. Mechanical forced,caused by interlocking of irregular shape particles
4. Electrostatic forces
5. Cohesive/Van der Waals forces
Evaluation of
powders Classification of powders :
Bulk Dusting Divided Insufflation
Parameters: Particle size analysis Angle of repose
Bulk density
Tapped density
Flowability
SEMISOLID DOSAGE FORMS
Evaluation of ointments
◦ Evaluation of creams
1. Rheology 2. Sensitivity 3. Stability
4. Physical appearance
Liquid Dosage Forms
Evaluation of syrups
• Visual inspection
➢Good looking
➢Elegance in appearance
•
pH measurement
•
Physical stability
Evaluation of elixirs
• Determination of alcohol content
• 5-40 %
• Viskosity measurement
• Stability
Evaluation of suspensions
• Sedimentation
• Rheological
• Electrokinetic; zeta potential → stability of disperse system
• Micromeritic → particle size of dispersed phase (for stability)
• Freeze thaw test →determine the tendency to crystallize or color
• pH measurement
• Visual inspection → good looking, elegance appearance
Evaluation of emulsions
•
particle size and particle count
•
Viscocity
•
Phase separation
•
Electroporetic properties
•
Electrical conductivity
Including
Determination of:
Evaluation of parenterals
• Leaker test
• Pyrogen test
• Sterility test
• Particulate evaluation
• Uniformity of content
Evaluation of eye drops
• Sterility
• Ocular toxicity and irritation
• Preservative efficacy
• Clarity
• pH
• In-vitro diffusion studies
• Determination of viscosity
Evaluation of Aerosol
• Flammability and combustibility
• Flash point
• Flame projection
•
Physicochemical characteristic
•
Performance
• Spray patterns
• Dosage with meter valves
• Net content
• Foam stability
• Particle size determination
•
Biological testing
• Therapeutic activity
• Toxicity
Physicochemical characteristic
Evaluation of nasal spray
• Appearance, clearance and clarity
• Drug content
• Impurities and degradation products
• Preservatives and stabilizing excipients assay
• Pump delivery
• Spray content uniformity
• Droplet size distribution
• Foreign particulate
• Microbial limit
• Preservative effectiveness
• Net content andweigth loss
• Leakage testing
• pH
Evaluation Cosmetic
Lipstick :
➢Surface anomalies
➢Thixotropic characteristics
➢Breaking point
➢Melting point
Evaluation of suppositoria
◦ Appearance
◦ Physical strength
◦ Melting range
◦ Uniformity of drug content
◦ Softening time
Evaluation of Novel DDS
→ Patch transdermal
◦ Physicochemical evaluation
◦ In-vitro evaluation
◦ In-vivo evauation
Physicochemical evaluation:
◦ Thickness
◦ Uniformity of weight
◦ Drug content
◦ Content uniformity test
◦ Moisture content
◦ Moisture uptake
◦ Flatness
◦ Tensile strength
◦ Peel adhesion
◦ Tack properties
◦ Thumb tack test
◦ Rolling ball test
◦ Quick stick
USP 35
EVALUATION OF DOSAGE FORMS
IN VIVO IN VITRO
IVIVC Methodology of characterizing the
physicochemical properties of a drug
substances as well as its associated drug product and discuss the relationship of these methods and properties to pharmacokinetic and pharmacodynamic properties of drug product
purposes
The ultimate goals:
• Understanding of relationship between the physicochemical and pharmacological properties of the drug substances to the pharmacokinetic and in-vitro performance of the drug product
• Development of the body of data that informs decision making relating to the formulation, manufacturing, and related regulatory activities necessary for the development, regulatory approval and marketing any of product
Bioavailability,
Bioequivalence, Dissolution
In-vitro evaluation:
• Physicochemical properties drug substances
• Physicochemical properties drug product
• Dissolution test
➢Immediated release DF
➢Extended release DF
In-vivo evaluation
• Characterization of drug substance
➢BCS
➢Pharmacokinetic
➢Pharmacodinamic
➢Drug disposition
• Characterization of the dosage form
