physical & chemical factors that affect’s drug’s biological performance roselyn...
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Physical & Chemical Factors that Affect’s
Drug’s Biological Performance
Roselyn Aperocho-NaranjoPharmacy Instructor
USPF, College of Pharmacy
Particle Size
How does Particle size How does Particle size affects drug affects drug absorption?absorption?
The decreasing size of drug particles will increase the surface area of the drug & will cause a rapid dissolution rate in a dissolution media.
Particle Size
However, the solubility does not significantly affect the particle size reduction or micronization in the manufacture of pharmaceutical agents.
Drug’s therapeutic effect depends on its particle size: Amphotericin, aspirin, bishydroxycoumarin,
chloramphenicol, griseofulvin, digoxin, fluocinolone acetonide, meprobamate, nitrofurantoin, phenobarbital, phenothiazine, phenylbutazone, prednisolone, penicillin, sulfadiazine, and tolbutamide.
Co-Solute & Complex Formation
The co-solute formation is concerned only with drugs having low solubility.
Processes of forming co-solutecompounds:1. Salting-out
Organic nonelectrolyte
dissolved
water
NaClNa
Cl
Precipitated organic nonelectrolye
Hydrated ions
Co-Solute & Complex Formation
The co-solute formation is concerned only with drug’s having low solubility.
Processes of forming co-solutecompounds:1. Salting-In
Undissolved organic electrolyte
water
Organic salt/AcidOr Salt of Ammonium
compounds
RCOOH
dissolved organic electrolyte
3. Clathrate FormationClathrate forming substances are: Gallic acid, urea, thiourea, amylose and zeolite
Drugs used in dissolving clathrates are:- Vitamin A, Sulfathiazole, chloramphenicol & reserpine.
Co-Solute & Complex Formation
Co-Solute & Complex Formation
4. Solid-in Solid Solution Complex
- is formed when a melted solid substance is mixed with another solid such as mannitol dissolved in succinic acid. These substances are rapidly dissolved in water.
Chemical Variation
Made for two reasons:1. change the strucutre of the active compound to increase pharmacologic response
2. maintain basic structure but the solubility is changed by the formation of either salts, ester, ether or other complex compounds.
Chemical Variation
Salt formation Electrolytes have higher solubility More rapidly dissolved/faster dissolution
rate than free acids & free bases In acidic drugs, dissolution rate increases
with increasing pH (salt formation)
• Esters- drugs dissolves at higher pH in the
small intestines- possess different rate of hydrolysis
Amorphous Crystalline Solids
Is more stable and have higher dissolution rate than the crystalline form
Example: PenG should not be used in amorphous form because it is more rapidly dissolved in the stomach fluid the crystalline form.
Anhydrous Form, Hydrates & Solvates
HydratesHydrates – are additon compounds of drugs with water
- dissolves more rapidly than the crystalline form
SolvatesSolvates – are addition compounds of drug and organic solvent
- dissolves faster than the non-solvated form
Polymorphism
Drug exist in different forms Exist only in a solid state Highest form of stability but lowest
dissolution rate When dissolution rate is high, stability
is low Can be stabilized by adding viscosity
increasing agents
Viscosity
Prolongs the diffusion time of solvent molecules
Disintegration & dissolution of drugs in tablet form is decreased with increasing viscosity
Food increases the viscosity of GIT content
Delay the absorption of drugs such as ethanol, salicylic acid, sulfonamides
Solubilizing Agents
Refers to Surface Active Agents (surfactants) The drug possess a hydrophilic and a
lipophilic ends, these will associate with the solvent molecule forming a colloidal solution
The associate ,molecules formed are called micelles or aggregates
Critical Micelle Concentration contains 50 to 150 molecules
If drug concentration is below the CMC, released rapidly
Solubilizing Agents
If drug concentration is below the CMC, released rapidly
If the CMC of the drug is high, drug release is affected
Examples are drug that are not diluted upon administration such as those given topically, rectally, intramuscularly and subcutaneous route
Solubilizing Agents
Drugs may have an increased bioavailability due to the surface active agents added
Include vitamin A, riboflavin, spironolactone and sulfisoxazole
Adsorption
Is the tendency of the substance to accumulate at a surface due to the unbalanced forces that causes the attraction of molecules on any surface.
Occur when the valence requirement of the molecule is bonded to adjacent molecules.
Adsorption
These attraction between adjacent molecules is called Van der waals force.
Adsorption & desorption occur rapidly Chemisorption occur when the valence
requirements of surface molecule are not fully met by the adjacent molecules.
Usually require heating to activate electron transfer
Example: Charcoal is used as antidote due to its adsorptive property.
Manufacturing Factors
Increased tablet compression and Increased amount of binders forced increased hardness of tablets and may prolong disintegration and dissolution time.
Increased amount of lubricants decrease hydrophilicity and wetting of tablets, also prolong disintegration and dissolution time
Manufacturing Factors
Increased amount of heat will cause suppositories to dissolve in the base which when cooled down,, it will form crystals and large needles thus prolonging the drug release
Summary
Different factors alter biological performance of drugs such as the rate and extent of drug release from the dosage form upon administration
Drugs should be in aquoues form except for rare cases of pinocytosis
Drug release can be determined in vitro by dissolution rate test for peroral and oral dosage forms and by dialysis for rectal and topical preparations
Summary
Drugs having different release characteristic reslts in different blood level curves in vivo
The difference in drug release is caused by the rates of drug release rather than the absorption pattern
Absorption rate is encountered in drugs with low solubility
Prepare on whole sheet of paper
Answer the following questions:How does the following factors affect the
release of drug from its original dosage form and solubility?
A. ClathratesB. Solid Amorphous FormsC. Chemical VariationD.