Biopharmaceutics Lecture 2 Notes PDF

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drug delivery, pharmaceutics...

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BIOPHARMACEUTICS Pharmacokinetics ● ●

The study of what the body does to a drug It is composed of the following processes − Absorption − Distribution − Elimination/excretion − Metabolism

Bioavailability ● ●

The EXTENT and the RATE to which a drug substance or its therapeutic moiety is delivered from a pharmaceutical form into the general circulation It can be broken down into 2 forms: − ABSOLUTE bioavailability – the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose − RELATIVE bioavailability – the amount drug from a formulation that reaches the systemic circulation relative to a different formulation

Biopharmaceutical Classification System (BCS) ● This is useful to know (not examined) if a drug is classed in group IV it is as if you are trying to dissolve ROCKS then the molecules POLYMORPH is studied which can change it to group III and in some cases II. ● Polymorph – the same chemical structure and pharmacodynamics but it has different physicochemical factors

pH Values of Different Body Compartments ● ● ● ● ● ●

Stomach pH = 1-3 Duodenum pH = 5-6 pH increases gradually in the jejunum Ileum pH = 7-8 Blood pH = 7.4 This is important as the way in which a drug is formulated is dependent on where in the body the drug is needed to be dissolved → absorbed

Transit of Pharmaceuticals in GI Tract: Stomach ● ●

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Gastric EMPTYING TIME = 5min – 2hrs Motility pattern is called INTERDIGESTIVE MYOELECTRIC CYCLE in fasting state Remember the DURATION of the phases

Metabolism – biotransformation

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Metabolites are formed after biotransformation and are generally MORE POLAR and therefore more easily IONISED compounds compared to the original drug, so these metabolites can be EXCRETED from the body easily The following organs perform biotransformation: − Liver (the most important organ for biotransformation) − Lungs − Kidney − GI System − Placenta − Adrenal glands − Skin − CNS − Blood Formulation Factors Affecting Oral Absorption

Solutions ●

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For drugs that are water soluble and chemically stable in Aq solution, formulation as a solution normally eliminates the dissolution step and presents the drug in the most readily available form for absorption However, when considering POORLY SOLUBLE drugs that have had their Aq solubility increased by creating a SALT for instance can result in the precipitation of the drug in the gastric fluid. Similarly the exposure of an Aq solution of a salt of a WEAK ACIDIC compound to gastric pH can also result in PRECIPITATION of the free acid from the drug In most cases the EXTREMELY FINE NATURE of the resulting precipitate permits a more rapid rate of dissolution than if the drug had been administered in other forms of oral dosage forms. But for some drugs this precipitation can have a major effect on BA This difference was shown in an EXPERIMENT where the same dose of a drug was given to dogs in 3 different solution formulation and they all had varying BA

Suspensions ● ● ●

These are useful for administering an INSOLUBLE or POORLY H2O SOLUBLE drug. The absorption of this dosage form is DISSOLUTION RATE LIMITED The oral administration of an Aq suspension results in a LARGE SURFACE area being immediately created in the stomach this facilitates dissolution and hence absorption. The following are factors that that are associated with the formulation of Aq suspension dosage forms that can influence BA of drugs from the GI tract − Particle size and effective SA of the dispersed drug − The crystal form of the drug − Any resulting complexation i.e. the formation of a non-absorbable complex between the drug and an excipient such as the SUSPENDING AGENT − The inclusion of a surfactant − The viscosity of the suspension

Liquid-Filled Capsules ● ●

POORLY H2O SOLUBLE drugs may exhibit greater bioavailability when placed into a capsule The release of the drug is affected by DISSOLUTION and B  REAKING OF THE SHELL

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Non-Aq vehicles can be either WATER-MISCIBLE in which case this will occur: − When it dissolves and/or disperses readily in the GI fluids liberating the drug as either a solution or fine suspension, which is then rapidly absorbed Non-Aq vehicles can also be WATER-IMMISCIBLE in which case this will occur: − Dispersion is facilitated by emulsifiers included in the vehicle, and also by BILE. Once dispersed the drug may end up as a SOLUTION, FINE SUSPENSION or NANO/MICROEMULSION. Drug has to then partition out of the oil droplet or absorbed by fat absorption process if it is digestible. The following are factors that that are associated with the formulation of Liquid-filled dosage forms that can influence BA of drugs from the GI tract − SOLUBULITY of drug in the vehicle − Particle SIZE of the drug (if suspended in the vehicle) − The NATURE of the vehicle i.e. hydrophilic or lipophilic (and whether the lipophilic vehicle is digestible or not) − The inclusion of a SURFACTANT − VISCOCITY and  COMPLEXATION  with excipients

Powder-Filled Capsules ● ● ●

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The BA of this dosage form is in some cases BETTER or the SAME as a tablet The rapid DISPERSION after the release creates a relatively large SA of drug to be exposed to the GI fluids DISSOLUTION RATE of a capsule formulation is dependent on dissolution rate of the shell, the rate of penetration of the GI fluid into the encapsulated mass, the rate of deaggregation of the mass and the dissolution rate of the particles. Penetration of GI fluids into the mass depends on: − EXCIPIENTS – hydrophilic excipients increase penetration rate − Pack DENSITY (and porosity) of the mass − WETTABILITY of the drug – which can be improved by a surfactant The following are factors that that are associated with the formulation of powder-filled dosage forms that can influence BA of drugs from the GI tract − The SURFACE AREA and particle SIZE of the drug − The use of the SALT form − The CRYSTAL form of the drug − The chemical STABILITY of the drug...