Pharmaceutical Dosage Forms

Dosage Forms Drug Delivery Systems, ADI + Excipients

Why Formulate?
1. Ease of Administration
2. Palatability
3. Stability
4. Improved appearance
5.
Major Types
SOLID DOSAGE FORMS
LIQUID DOSAGE FORMS
SEMI-SOLID DOSAGE FORMS

Instabilities
A. Chemical
B. Microbial

A. Chemical
Hydrolysis

()
ASA
Pen G (Benzyl Penicillin - -lactam ring destroyed)
Pen V (Bibig, Oral)
Oxidation
Air, Trace metals, Light
EDTA to chelate metals
Antioxidants
oil soluble BHA, BHT, L-tocopherol or Vitamin E
water soluble Ascorbic Acid, Butylated hydroxyanisole, anisole = toluene

B. Microbial
1. Personnel
2. Equipment
3. Raw Material
4. Packaging Material

USP requirement <1111>
Oral : Absence of Escherichia coli
Topical: Absence of Pseudomonas aeruginosa (blindness), Staphylococcus aureus
Natural Products: Absence of Salmonella
**Can be seen in emulsions (crack if there is microbial degradation of emulsifying agent

Route of Administration (ROA)
Term Site
Oral GIT
Sublingual Under the tongue
Buccal Bucal sulcus
Topical Local effect on skin
Transdermal Systemic absorption
Intraocular Eye
Intranasal Nose
Inhalational Lungs
Rectal Rectum
Vaginal Vagina
Parenteral
Para enteral (outside enteral tract)
IV, IM, SubQ or SL, Intradermal
Outside GIT

SOLID DOSAGE FORMS

Powders Intimate mixtures of finely divided drugs in the dry form

Advantages:
Flexibility in dosing
Relatively stable

Disadvantages:
Patient misunderstanding
Inconvenience
Taste

Two types:
1. Bulk powders
o Dentrifices to clean pustiso (powder in water), not used for potent drugs
o Douche direct to body cavities (i.e. Vaginal douches)
o Antacids
o Dusting powders Johnson Baby Powder
2. Divided powders
o Chartulae (Latin term) Chart
o Paper tabs papelitos
o Powders that are in individual paper tablets
o Papers used in paper tablets:
a. Bond paper no moisture resistance, opaque
b. Glassine paper limited moisture resistance, glazed, transparent
c. Vegetable parchment limited moisture resistance, thin, semi-opaque
d. Waxed paper moisture resistant and water proof (suitable for hygroscopic and deliquescent powders)
Hygroscopic absorb water, does not liquefy
Deliquescent absorb water, liquefies

Methods of comminution:
A. Small Scale
1. Trituration exposing substance to the rigors of mortar and pestle

Types of Mortar and Pestle:
a. Glass used for substances that stain, mixing solutions.
b. Porcelain suitable for soft aggregates and crystalline solids
c. Wedgewood same as above

2. Levigation
o used in preparations of ointments
o formation of a paste through addition of non-solvent such as levigating agent (must not dissolve in API)
e.g. sulfur ointment (sulfur + mineral oil) *gritty feeling

3. Pulverization by intervention comminution facilitated by the addition of a volatile solvent
e.g. camphor and alcohol
I
2
crystal and ether

B. Large Scale
o For manufacturing
1. Mills
2. Pulverizers





Reasons for particle size reduction affects:
1. Dissolution rate
2. Bioavailability (Micronization)
3. Suspendability
4. Grittiness
5. Uniformity of dosage units

Blending:
A. Small Scale
1. Spatulation blending with spatula, non-potent substance and eutectic mixture (with inert diluent)
2. Sifting - blending with sifts, light and fluffy product, non-potent
3. Trituration for potent : Geometric dilution
e.g. 0.5 g API + 0.5 g diluent = 1 g
1 g mix + 1 g diluents = 2 g
2 g mix + 2 g diluents = 4 g

Eutectic mixture Inert diluent
Menthol and thymol MgO
Phenor and camphor

B. Large Scale
Tumbling - enclosure of mixture in a rotating chamber

Granules