pharmaceutics and biopharmaceutics
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Pharmaceutics and Biopharmaceutics
Manufacturing Versus Compounding
Manufacturing1. Utilizes large-scale
production manufacturing plants
2. Regulated NDAs/ANDAs to market
Compounding1. Practiced using small-
size equipment in small pharmacy areas
2. Requires a prescription. Compounded prescriptions are exempt from NDAs.
Manufacturing Versus Compounding
Manufacturing3. Manufacturers have
extended patent protection for chemical patents, process patents, and use patents.
4. Manufactured products are designed to meet the vast majority of patient needs (97%-99%)
Compounding3. Pharmacists generally
have no patent protection.
4. Compounding meets unique needs (often critical) for very small patient populations (1%-3%).
Biopharmaceutics
“ The Biologic response to a drug is the result of an
interaction between the drug substance and functionally important cell receptors or
enzyme systems.”
Biopharmaceutics
“ The area of study embracing this relationship between the physical,
chemical and biological substances as they apply to drugs, dosage
forms, and to drug action is termed BIOPHARMACEUTICS.”
Biopharmaceutics
Requirements for a drug to exert its biological action:1. It must be transported by the body fluids.2. It must traverse the required biologic membrane barriers.3. It must escape widespread distribution to unwanted
areas.4. It must endure metabolic attack. 5. It must penetrate in adequate concentration to the sites
of action.6. It must interact in a specific fashion, causing an alteration
of cellular function.
Biopharmaceutics
• Pharmacokinetics versus Pharmacodynamics
• ADME• Absorption – uptake into the circulation• Bioavailability – rate and extent of systemic
absorption• Question: 100% absorbed = 100% bioavailable?
Bioavailability data
1. The amount or proportion of drug absorbed from a formulation or dosage form
2. The rate at which the drug was absorbed3. The duration of the drug’s presence in the
biologic fluid or tissue; and, when correlated with patient response
4. The relationship between drug blood levels and clinical efficacy and toxicity
Terms Used To define The Type or Level Of “Equivalency” Between Drug Products
Pharmaceutical Equivalents -are drug products that contain identical amounts of the identical active ingredient.
Example: the same salt or ester of the same therapeutic moiety
Pharmaceutical Alternatives - are drug products that contain the identical therapeutic moiety, or its precursor, but not necessarily in the same amount or dosage form or as the same salt or ester.
Bioequivalent Drug Products - are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption
do not show a significant difference when administered at the same molar dose of the therapeutic moiety under similar experimental conditions, either single dose or multiple dose.
Terms Used To define The Type or Level Of “Equivalency” Between Drug Products
Therapeutic Equivalent - has been used to indicate pharmaceutical equivalent which, when administered to the same individuals in the same dosage regimens, will provide essentially the same therapeutic effect.
The most common experimental plan to compare the bioavailability of two drug products is the
simple crossover design study.
(12 to 14 individuals, males between 18 to 40 years, same height and weight)
Biopharmaceutics
Identification of a new drug entity Pre – Clinical Stage Clinical Stage
– Phase I - “Is the drug safe?”– Phase II - “Does the drug work?”– Phase III - “How well does it work?”– Phase IV - Post marketing studies
Route of administration
* Local versus systemic effects1. Oral2. Sublingual3. Parenteral
i. Intravenousii. Intrarterialiii. Intracardiaciv. Intraspinal
Routes of Administration
v. Intraosseousvi. Intradermalvii. Subcutaneous (2 mL or less) - forearm, upper arm, thigh or natesviii. Intramuscular (2 – 5 mL) – gluteal or lumbar
4. Epicutaneous5. Transdermal6. Conjunctival7. Intraocular8. Intranasal9. Rectal10. Vaginal11. Urethral
Rationale for Dosage Form Design
1. Mechanism for safe and convenient delivery of drug2. Protection from destructive factors3. Masking of taste and odor4. Appropriate liquid dosage forms5. Rate – controlled drug action6. Insertion into body orifices7. Optimal drug action from topical administration or
through inhalation therapy8. Placement of drugs directly into bloodstream
Dosage Forms
Tablets Capsules Solutions Suspensions Syrups Modified – release dosage forms
– Controlled – release, sustained action, long acting, timed release, timed delay, sustained action
Parenteral Products
Administered directly into the bloodstream or a specific organ / area
General types:1. Drug injection
2. Drug for injection
3. Drug injectable emulsion
4. Drug injectable suspension
5. Drug for injectable suspension
Parenteral Drugs
Advantages:
1. When rapid drug action is desired
2. When patient is uncooperative, unconscious or unable to accept or tolerate oral medication
3. When drug is ineffective by other routes
Parenteral Drugs
Disadvantages:
1. Pain factor
2. Requires administration by a healthcare professional
3. Immediate occurrence of toxic effects
4. Difficult removal from the body
5. More expensive
Timan-i
Body fluids are more receptive to drugs in aqueous vehicle than in oily one.
Slow absorption means prolonged drug action– Depot or repository injection
Requirement: Sterility
Parenteral Drugs
Solvents and Vehicle for Injections:1. Water for Injection, USP
- purified by distillation or by reverse osmosis- pyrogen-free but not required to be sterile
2. Sterile Water for Injection, USP- sterilized and packaged in single – dose containers- pyrogen-free
3. Bacteriostatic Water for Injection- sterile water for injection containing one or more suitable
antimicrobial agents (benzyl alcohol)
Parenteral Drugs
Solvents (Continuation) Normal Saline Solution (NSS) Bacteriostatic NSS 5% Dextrose in water Ringers / Lactated Ringer’s Solution (KCl,
NaCl, CaCl2 + Na Lactate)
DOSAGE FORM/DRUG DELIVERY SYSTEM APPLICATION
Route Of Administration Primary Dosage Forms
oral tablets, capsules, solutions, syrupselixirs, suspensions,magmas, gelsand powders
sublingual tablets, troches or lozenges
parenteral solutions, suspensions
epicutaneous/transdermal ointments, creams, infusion pumpspastes, plasters, powders, aerosolslotions, transdermal patches, discs
conjunctival contact lens inserts, ointments
intraocular/intraaural solutions, suspensions
intranasal solutions, sprays, inhalants, oint.
Intrarespiratory aerosols
DOSAGE FORM/DRUG DELIVERY SYSTEM
APPLICATION
Route Of AdministrationPrimary Dosage Forms
rectal solutions, ointments, suppositories
vaginal solutions, ointments, emulsion foams, tablets, inserts, suppositories, sponge
urethral solutions, suppositories
Routes Of Drug Administration
TERM SITE
oral mouth
peroral (per os, p.o.) gastrointestinal tract via mouth
sublingual under the tongue
parenteral other than GIT (by injection)
intravenous vein
intraarterial artery
intracardiac heart
intraspinal/intrathecal spine
intraosseous bone
intraarticular joint
intrasynovial joint-fluid area
intracutaneous/intradermal skin
subcutaneous beneath the skin
intramuscular muscle
Routes Of Drug Administration
TERM SITE
epicutaneous (topical) skin surface
transdermal skin surface
conjunctival conjunctiva
intraocular eye
intranasal nose
aural ear
intrarespiratory lung
rectal rectum
vaginal vagina
urethral urethra
Factors Affecting Dosage Form Design
1. Physical and Chemical properties of the drug2. Dose of the drug3. Intended route of administration4. Type of drug delivery system desired5. Desired therapeutic effect6. Physiologic release of drug at absorption site7. Pharmacokinetics and Pharmacodynamics of
the drug* Also holds true in compounding
Factors That Determine A Dosage Regimen
Activity, ToxicityPharmacoknetics
Minimum therapeutic dose Absorption
Toxic Dose Distribution
Therapeutic index Metabolism
Side effects Excretion
Dose-response relationship
Clinical Factors Other Factors
Clinical State of patientManagement of Therapy
Age, weight, urine pH Multiple drug therapy Tolerance-dependence
Condition being treated Convenience of regimen Pharmacogenetics-
idiosyncrasy
Existence of other disease states Compliance of patient Drug interactions
DosageRegimen
Containers
1. Ampoule / Ampul / Ampoul- Sealed by fusion of the glass containers under aseptic
condition- Neck portion that easily separates from the body of the
container without fragmentation of the glass- Once opened, any unused portion may not be retained and
used at a later time
2. Vials- With rubber closures to permit the penetration of a
hypodermic needle without the removal or destruction of the closure.
- Resealable
3. Pre – filled syringes
Pagbantay!
Because it is impossible in practice to transfer the entire volume of a single –
dose container, slight excess in volume of the content over the labeled size or volume of the
package is permitted.
Topical Preparations
Drugs should penetrate and be retained in the skin for a period of time
Treatment is based on qualitative measures Factors that affect product type and selection
of appropriate base:– Emollient and Occlusive effects– Ease of application and removal
Ointments, creams, pastes (greater occlusive property and useful in serous discharges)
How A Drug Passes Through The Body
1. Absorption = The site at which a drug enters the body affects its rates of absorption
a. Skin c. Digestive Tract
b. Lungs d. Bloodstream
2. Distribution = Most drugs enter the bloodstream; many are then distributed to
cells of various organs
a. Bone e. Glands
b. Nerves f. Heart
c. Muscles g. Cells
d. Brain h. Other organs
3. Metabolism = A drug is partially broken down, usually in the liver, before or after distribution
a. Liver
4. Elimination = Finally, a drug is eliminated, mainly via kidneys, but also in stools
and tears or through breathing
a. Breast milk c. Tears
b. Saliva d. Sweat
Some Factors Which Can influence The Bioavailability Of Orally Administered Drugs
I. Drug Substance Physiochemical Properties
II. Pharmaceutical Ingredients and Dosage Form Characteristics
III. Physiologic Factors and Patient Characteristics
Some Factors Which Can influence The Bioavailability Of Orally Administered Drugs
I. Drug Substance Physiochemical Properties
A. Particle Size
B. Crystalline or Amorphous Form
C. Salt Form
D. Hydration
E. Lipid/Water Solubility
F. pH and pKa
Some Factors Which Can influence The Bioavailability Of Orally Administered Drugs
II. Pharmaceutic Ingredients and Dosage Form Characteristics
A. Pharmaceutical Ingredients
1. Fillers 7. Surface Active Agents
2. Binders 8. Flavoring Agents
3. Coatings 9. Coloring Agents
4. Disintegrating Agents 10. Preservative Agents
5. Lubricants 11. Stabilizing Agents
6. Suspending Agents
Some Factors Which Can influence The Bioavailability Of Orally Administered Drugs
B. Disintegration Rate (Tablets)
C. Dissolution Time of Drug in Dosage Form
D. Product Age and storage Conditions
III. Physiologic Factors and Patient Characteristics
A. Gastric Emptying Time
B. Intestinal Transit Time
C. Gastrointestinal Abnormality or Pathologic Condition
D. Gastric Contents
1. Food
2. Other Drugs
3. Fluid
E. Gastrointestinal pH
F. Drug Metabolism (gut and during first passage through liver)