A primary concern in biopharmaceutics is the bioavailability of drugs.

Biopharmaceutics – refers to the measurement of the rate and extent of active drug that
reaches the systemic circulation; means access to the blood stream
Pharmaceutical Factors Affecting Drug Bioavailability:
1. Type of the drug product
2. Nature of excipients in the drug product
3. Physico-chemical properties of the drug
- Measurable characteristics by which a compound interacts with other system
Physico-Chemical Properties of the Drug
1. Particle size of a drug in a solid dosage form
- In order to affect dissolution rate based on one’s objective, there should be a
change in particle size
- Particle size larger surface are to be wetted dissolution rate faster
rate of absorption
- But for local effect, increased particle size is required
2. Particle size of a dispersed phase in an emulsion
o 2-phase system in which one should be uniformly dispersed into another
o Dispersed phase should be in small particle size so it can readily mix with
dispersion medium
3. Tablet disintegration
 Disintegration is the physical break-up of an intact dosage form to its
component aggregates
 Disintegration depends on the disintegrant used
 Starch
 Microcrystalline cellulose
 It was generally recognized some years ago that a solid drug product had
to disintegrate into small particles and release the drug before
absorption could take place
 For the purpose of monitoring tablet disintegration, USP established an
official disintegration test.
 Solid products exempted from disintegration tests
 Troches
 Tablets which are intended to be chewed
 Drug products intended for SR, or prolonged or repeat action
 Separate specifications are given for
 Uncoated tablets
 Plain coated tablets
 Enteric coated tablets
 Buccal tablets
 Sublingual tablets
4. Tablet capsule & adjuncts
 Excipients
 Added to the active ingredient to form a dosage form that is convenient for
control purposes
  It should be inert, inactive, neither enhances nor diminishes the therapeutic
effect of the drug
 Diluents – added to increase the bulk/mass of the dosage form
Ex. Lactose, dibasic Ca phosphate, starch, microcrystalline cellulose
 Binder – makes the diluent adhere to the tablet to form a compact mass. Pressure is
applied to make the tablets contact
Ex. Acacia, alginic acid, gelatin, povidone, etc.
 Lubricant – helps to have an easier transfer from one stage of manufacture to
another
Ex. Magnesium strearate, stearic acid, talc, hydrogenated vegetable oil
Excessive magnesium stearate (a hydrophobic lubricant) in the formulation may retard drug
dissolution and cause slower drug absorption
5. Tablet coating
 Protection;
 Uneven coating can cause uneven release of active ingredient
Ex. A. enteric coatings – employed to permit safe passage of tablet thru the acid
environment of the stomach where certain drugs may be destroyed, to the more
suitable juices of the intestines where tablet dissolution safely takes place. (shellac,
cellulose acetate phthalate)
B. film-coatings – employed to protect the drug substance from the destructive
influences of moisture, light and air throughout their period of storage or to conceal
a bad or bitter taste from the taste buds of the patient.
(hydroxypropylmethylcellulose)
C. sugar-coatings – conceal bitter taste (liquid glucose, sucrose)
D. surfactants – low conc of surfactant = decrease surface tension = rate of
dissolution?
High conc of surfactant = formation of micelles = rate of dissolution?
6. Crystalline drug properties
 Polymorphism – refers to the arrangement of a drug in various crystal forms or
polymorphs
 Polymorphs – have the same chemical structure but different physical properties
such as: solubility, density, hardness and compression characteristics
 Some polymorphic crystals may have much lower aqueous solubility than the
amorphous forms, causing a product to be incompletely absorbed.
Ex. Chloramphenicol
 Crystal have the lowest free energy is stable
 Solute
Drug + solvent = crystal
Hydrates
Drug + H2O = crystal
 In general, the crystalline form of drugs are more rigid and thermodynamically more
stable than the amorphous form. The crystal form with the lowest free energy is the
most stable polymorph.
  A change in crystal form may cause problems in manufacturing the product. For
example, a change in crystal structure of the drug may cause cracking in a tablet or
even inability for a granulation to be compressed to form a tablet
 Erythromycin dehydrate dissolves faster than the monohydrate & anhydrous form
 Less hydrated – faster dissolution
 Ampicillin anhydrous would have faster dissolution that trihydrate but is less
absorbed
 Clathrates – cages the drug to make it more stable (protective) and soluble (reacts
with the solvent)
e.g. gallic acid, urea, zeolite
DRUGS WITH NARROW THERAPEUTIC WINDOW
 Size of dose (mg/kg)
 Dosing frequency (bid, tid, od)
SIZE OF THE DOSE
Determined by:
 Inherent potency of the drug
 Dosing strengths
e.g. score in tablets for fractured dosing. Paper tablets
DOSING FREQUENCY
Dependent on:
o Clearance of the drug (elimination)
o Target plasma drug concentration (MEC)
e.g. drug with short half-life or rapid clearance how frequent is the dosing?
SUSTAINED RELEASE (SR) TABETS
o Devised to minimize fluctuating plasma concentration and good patient compliance
ROUTE OF ADMINISTARTION
o Formulation given in IM, IV and orally only changes the rate of absorption but NOT the
rate of elimination
o Sublingual rapid onset but shorter duration of action