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1. BIOPHARMACEUTICS & PHARMACOKINETICS
2. Bio – life
Pharmaceutics
– general area of study concerned with
the formulation, manufacture, stability
and effectiveness of pharmaceutical
dosage forms.
3. Biopharmaceutics study of the factors influencing the bioavailability of a drug in man and animals and the use of this information to optimize pharmacological or therapeutic activity of drug products in clinical application.
4. Biopharmaceutics
study of the influence of formulation on therapeutic activity of a drug product.
5. Biopharmaceutics study embracing this relationship between the physical, chemical and biological sciences as they apply to drugs, dosage forms, and to drug action.
6. Biopharmaceutics
Modern biopharmaceutics is the study of the relationship of the physico-chemical properties and in vitro behavior of the drug and drug product on the delivery of the drug to the body under normal or pathologic conditions.
7. Drug agent intended for use in the diagnosis, mitigation, treatment, cure or prevention of disease in man or in other animals.
It may be:
1. synthetic 4. biological
2. semi-synthetic 5. natural
3. chemical
8. Drug Modern drugs are potent chemical substances that must be fabricated into a drug product before use.
Generally, the drug is combined with other ingredients into a drug formulation, which may be a solution, tablet, capsule or suppository.
9. Rationale The development of biopharmaceutic principles allowed for the rational design of drug products, which would enhance the delivery of active drug, and optimize the therapeutic efficacy of the drug in the patient.
10. Drug Product a finished dosage form that contains an active drug ingredient generally, but not necessarily, in association with inactive ingredient.
formulation or matrix in which the drug is contained
The term may also include a dosage form that does not contain an active ingredient intended to be used as placebo.
11. Drug Action result of an interaction between the drug substance and functionally important cell receptors or enzyme systems.
This response is due to the alteration in the biologic processes that were present prior to the drug administration.
12. In vitro – glass
referring to a process or reaction carried out in a culture dish or test tube
In vivo – in the living organism
13. Effects of Biopharmaceutics Generic equivalency
Drug availability
Therapeutic efficacy
Drug substitution
14. BIOPHARMACEUTICS & PHARMACOKINETICS
15. Effects of Biopharmaceutics Drug product selection
*drug product should be cost-effective
*drug product selection should be according to the patient’s capability
*drug product selection should be based upon the patient’s diagnosis
16. Aim The aim of biopharmaceutics is to adjust the delivery of drug to the general circulation in such a manner as to provide optimal therapeutic activity for the patient.
17. Aim Biopharmaceutic studies allow drugs to be formulated rationally based on pharmaceutic properties.
18. Some Pharmaceutic Properties Some drugs are intended for topical or local therapeutic action at the site of administration. For these drugs, systemic absorption is undesirable.
19. Some Pharmaceutic Properties
Drugs intended for local activity generally have a direct pharmacodynamic action without affecting other body organs. These drugs may be applied topically to the skin, nose, eyes, mucous membranes, buccal cavity, throat and rectum.
20. Factors Affecting Biopharmaceutics a. physical state of the drug
- according to the 4 states of matter
The crystal or amorphous forms and/or the particle size of a powdered drug have been shown to affect the dissolution rate, and thus the rate of absorption, for a number of drugs.
21. Factors Affecting Biopharmaceutics
By selective control of the physical parameters of a drug, biologic response may be optimized.
22. b. dosage form - delivery system the drug could be available or administered.
23. b. dosage form Each of dosage unit is designed to contain a specified quantity of medication for ease and accuracy of dosage administered.
Each product is a formulation unique unto itself
24. Biopharmaceutic considerations often determine the ultimate dose and dosage form of a drug product.
25. Biopharmaceutic considerations often determine the ultimate dose and dosage form of a drug product.
For example, the dosage for a drug intended for local activity, such as a topical dosage form, is often expressed in concentration or as % of the active drug in the formulation.
26. The amount of drug is not specified because it is the concentration of the drug at the active site that relates to the pharmacodynamic action.
27. Biopharmaceutics Biopharmaceutic studies must be performed to ensure that the dosage form does not irritate, cause an allergic response or allow systemic drug absorption.
28.
29. c. route of administration each route of drug application presents special biopharmaceutic considerations in drug product design.
30. c. route of administration by carefully choosing the route of drug administration and properly designing the drug product, the bioavailability of the active drug can vary from rapid and complete absorption to a slow, sustained rate of absorption or even virtually no absorption, depending on the therapeutic objective.
31. Example The design of a vaginal tablet formulation for the treatment of a fungus infection must consider ingredients compatible with vaginal anatomy and physiology.
32. Example An eye medication may require special biopharmaceutic considerations including appropriate pH, isotonicity, local irritation to the cornea, draining by tears, and concern for systemic drug absorption.
36. Pharmaceutic 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 systems
37. Physico-Chemical Properties of the Drug 1. Particle size of a drug in a solid dosage form
2. Particle size of a dispersed phase in an emulsion
3. Tablet disintegration
4. Tablet & capsule adjuncts
5. Tablet coating
6. Crystalline drug properties
38. Something to ponder….
39. 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 area to be wetted ? ? dissolution rate ? faster rate of absorption
But for local effect, increased particle size is required
40. 2. Particle size of the dispersed phase in an emulsion 2-phase system in which one should be uniformly dispersed into another.
Dispersed phase should be in small particle size so it can readily mix with dispersion medium.
41. 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
42. 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.
43. USP Specifications Separate specifications are given for
uncoated tablets
plain coated tablets
enteric coated tablets
buccal tablets
sublingual tablets
44. USP Specifications Solid drug products exempted from disintegration tests
Troches
Tablets which are intended to be chewed
Drug products intended for SR, or prolonged or repeat action
45. 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
46. Roles/Effects of Excipients may affect drug absorption
may increase solubility
may increase retention time of drug in the GIT
may act as carriers to increase diffusion across intestinal wall
In contrast, most excipients may retard drug dissolution and decrease drug absorption
47. Different Excipients used in Tablets 1. Diluents – added to increase the bulk/mass
of the dosage form
ex. Lactose, Dibasic Ca Phosphate, starch,
microcrystalline cellulose
2. 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.
48. Different Excipients used in Tablets 3. Lubricant
– helps to have an easier transfer from one stage of manufacture to another
- assist the smooth tableting process.
Ex. Mag. Stearate, stearic acid, talc, hydrogenated vegetable oil
excessive magnesium stearate (a hydrophobic lubricant) in the formulation may retard drug dissolution and cause slower drug absorption.
49. 5. Tablet Coating protection
uneven coating can cause uneven release of active ingredient
Example:
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)
50. 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)
51. 4. Surfactants
Low conc. of surfactant = decrease surface tension = rate of dissolution?
High conc. of surfactant = formation of micelles = rate of dissolution?
52. 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
53. Some polymorphic crystals may have much lower aqueous solubility than the amorphous forms, causing a product to be incompletely absorbed.
Ex. Chloramphenicol
Crystal with the LOWEST free energy is stable
54. Solvate
Drug + solvent = crystal
Hydrates
Drug + H2O = crystal
55. 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.
56. Example Erythromycin dehydrate dissolves faster than the monohydrate & anhydrous form
less hydrated – faster dissolution
Ampicillin anhydrous would have faster
dissolution than trihydrate but it is less absorbed
57. Clathrates- cages the drug to make it more stable (protective) and soluble (reacts with the solvent)
e.g. gallic acid, urea, zeolite
58. Drugs with narrow therapeutic window Size of dose (mg/kg)
Dosing frequency (bid, tid, od)
59. Size of the dose Determined by:
Inherent potency of the drug
Dosing strengths
E.g. score in tablets for fractured dosing. Paper tablets
60. Dosing frequency Dependent on:
Clearance of the drug (elimination)
Target plasma drug concentration (MEC)
e.g. Drug with a short half-life or rapid clearance ? how frequent is the dosing?
61. Sustained release (SR) tablets Devised to minimize fluctuating plasma concentration and good patient compliance
62. Route of administration Formulation given in IM, IV and oral only changes the rate of absorption but NOT the rate of elimination
Sublingual ? rapid onset but shorter duration of action
63. Maraming salamat po
