PHPhyPhar (Lecture) | Module 1: INTRODUCTION TO PHYSICAL PHARMACY

Physical Pharmacy

Deals with the physicochemical principles underlying dosage forms and drug delivery systems’ design and manufacture, and drugs’ bioavailability.

Physical Pharmacy

It is the study of the physical and chemical properties of the drug.

Physical Pharmacy

Entails the formulation of the drug itself

Biopharmaceutics

The study of the physical and chemical properties of drugs and their proper dosage as related to the onset, duration, and intensity of drug action. After making the drug, we will already apply it in life, “bio”

Biopharmaceutics

This starts from the Liberation and ends with the Response

Liberation

Biopharmaceutics starts from the ________ and ends with the Response

Response

Biopharmaceutics starts from the Liberation and ends with the ________

Liberation

BIOPHARMACEUTICS: Setting the drug free

Absorption

BIOPHARMACEUTICS: movement of the free drug to your systemic circulation

Distribution

BIOPHARMACEUTICS: to the site of action or the rest of the body

Metabolism

BIOPHARMACEUTICS: you will digest the drug → making it less toxic

Elimination

BIOPHARMACEUTICS: you will excrete the drug

Pharmacodynamics

entails the response of the drug

• The effect of the drug, either toxic or theurapeutic effect.

Drug Dosage Forms

Suspension

DRUG DOSAGE FORMS: solid particle in liquid form.

• Either a colloid, an amorphous drug, or a crystalline drug.

Syrups

DRUG DOSAGE FORMS: same as suspension, but it has sugar content for preserving the drug.

• Sucrose, a monosaccharide and a disaccharide, can preserve the drug

Suppositories

DRUG DOSAGE FORMS: inserted via the rectum or vagina

Tablets

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals in a compressed powder

Capsules, Powder-Filled

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals in a noncompressed powder - hard gel capsules

Capsules, Liquid-Filled

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Molecules or crystals in vegetable oil - Ex. Advil

Suppositories

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals in waxy, water miscible, or water-immiscible base

Solutions

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Molecules

Suspensions

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals in an aqueous or nonaquous liquid

Ointments

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals or molecules in a semi-solid oleaginous base

Creams

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals or molecules in water, miscible or immiscible, semisolid cream base

Gels

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crytals or molecules in a water-miscible semi-solid gel base

Aerosols

COMMON STATE OF THE DRUG IN THE DOSAGE FORM: Crystals or molecules in a gas, liquid or semisolid

Oral

ROUTES OF DRUG ADMINISTRATION: tablet

Inhaler

ROUTES OF DRUG ADMINISTRATION: by mouth/nose

Sublingual

ROUTES OF DRUG ADMINISTRATION: under the tongue

Buccal

ROUTES OF DRUG ADMINISTRATION: side of the cheeks

Rectal

ROUTES OF DRUG ADMINISTRATION: rectum

Topical

ROUTES OF DRUG ADMINISTRATION: skin

Otic

ROUTES OF DRUG ADMINISTRATION: ears

Optic

ROUTES OF DRUG ADMINISTRATION: eyes

IV

PARENTERALS, INJECTIONS: 25°

IM

PARENTERALS, INJECTIONS: 90°

Intraarterial

PARENTERALS, INJECTIONS: arteries

Subcutaneous

PARENTERALS, INJECTIONS: 45° (ex., Insulin, pinch the skin)

Intradermal

PARENTERALS, INJECTIONS: dermis

15

INTRADERMAL: How many degrees when the skin is thick?

10

INTRADERMAL: How many degrees when the skin is thin?

Enteral

Consists of:

• Oral

• Rectal

Injection

Consists of:

• Intravenous

• Intraarterial

• Intramuscular

• Subcutaneous

• Intraosseous

• Intrathecal

Parenteral

Consists of:

• Intravenous

• Intraarterial

• Intramuscular

• Subcutaneous

• Intraosseous

• Intrathecal

• Inhalation

• Topical

• Transdermal

• Sublingual

• Nasal

Enteral

• will pass the GIT

• There is a higher incidence that the drug will be metabolized by the LIVER.

Liver

ENTERAL: It will pass the GIT and there is a higher incidence that the drug will be metabolized by the?

Hepatic First Pass Metabolism

ENTERAL: This is where the drug is metabolized before inducing its effects. 50% of the drug will be metabolized and will be excreted, 50% - produce the therapeutic effect.

Parenteral

• will bypass the GIT

• injections

• Almost of the local drugs like inhalers, topical ointments, and transdermal patches

Parenteral

• It was invented to cancel the first-pass metabolism

IV

PARENTERAL: since the drug will be directly administered to the veins, it means it is 100% bioavailable

Parenteral

Some situations require _________ drugs to produce immediate effects

Inferior Rectal Vein, Middle Rectal Vein, and Superior Rectal Vein

There are 3 types of rectum vents

Inferior Rectal Vein

• Will proceed to the inferior vena cava

• Vena cava - direct to heart

Middle Rectal Vein

• Will proceed to the inferior vena cava (bypassing liver metabolism)

• Ideal location for inserting the suppository

Middle Rectal Vein

• Goal in administering drugs - to produce their therapeutic effects

• As much as possible, you will bypass the metabolism

• wall of the rectum, perfect body temperature to make suppository melt (ADJACENT TO ANUS)

Superiod Rectal Vein

• Will lead to the inferior mesenteric vein

• It will be directed to the liver (for metabolism)

Mesenteric Vein

• The superior rectal vein drains the upper part of the rectum and continues as the inferior?

Liver

Primary organ where metabolism happens—makes the drug less toxic or non-toxic at all → will dissolve in urine

Kidney

Primary organ for excretion

Urine

Waste product from kidney, have higher water content → they will be EXCRETED

Urine

Since “like dissolves like,”; polar drug will be dissolve in the?

Bioavailability

The proportion (percent or fraction) of an administered dose of unchanged drug that reaches the systemic circulation.

Bioavailability

Tablet by oral → liberated in small intestine → absorbed in the stomach

Bioavailability

The fraction of the unchanged drug that will reach the circulation

100%

BIOAVAILABILITY: What is the bioavailability of IV?

30% or 50%

BIOAVAILABILITY: What is the bioavailability of PO?

PO

BIOAVAILABILITY: this will pass through the GIT

Liberation, Absorption, Distribution, Metabolism and Excretion

DRUG DISPOSITION

Liberation

DRUG DISPOSITION:

• release of the drug from its dosage form into the body fluids

  • Saliva, urine, sweat, blood,

  • The drug must be dissolved in stomach acid (HCl) or the gut

• Some drugs that are not well formulated here

Absorption

DRUG DISPOSITION:

• into the bloodstream - rate-limiting steps

• How will it get into circulation

Rate-Limiting Steps

ABSORPTION:

• It will limit the absorption or delay the therapeutic effect

• Layer of cells - delays the absorption

  • In the stomach there is a single layer of columnar cells

  • GUT - have enterocytes

Distribution

DRUG DISPOSITION:

• to various parts of the body, especially to the site of action

• Where it will go

Metabolism

DRUG DISPOSITION:

• by enzymes - First-Pass Metabolism

• How it will be broken down

Phase 1 Metabolism and Phase 2 Metabolism

DRUG DISPOSITION:

• convert the drug into its polar form (water-loving)

Functionalization

METABOLISM: PHASE 1 REACTION is called as?

Phase 1 Metabolism

METABOLISM: Add or uncover a polar group in the drug molecule

Conjugation

METABOLISM: PHASE 2 REACTION is called as?

Phase 2 Metabolism

METABOLISM: Will covelently bond (add) a polar functional group

Excretion

DRUG DISPOSITION:

• elimination through the kidneys or other routes

  • Skin - sweat/perspiration waste product

  • Lungs - carbon dioxide

  • GIT - feces

• How will it be removed from the body

Skin

EXCRETION: sweat/perspiration waste produc

Lungs

EXCRETION: carbon dioxide

GIT

EXCRETION: feces

Solid State Properties

PHYSICOCHEMICAL PROPERTIES OF THE DRUG: Most of the drugs are either in crystalline form or Amorphous form

Crystalline

PHYSICOCHEMICAL PROPERTIES OF THE DRUG: has a regular repeating unit called a lattice, which is why they were able to mold forms like a diamond and rock salt.

Amorphous

PHYSICOCHEMICAL PROPERTIES OF THE DRUG:

• have irregular to regular repeating units

• Do not have the order

• Ex. glass (when broken, it is more like a powder than a crystal)

Crystalline

Amorphous

Amorphous

CHEMICAL NATURE: Isotropic

Crystalline

CHEMICAL NATURE: Anisotropic

Ionized and/or Nonionized

• Most drugs are weak acids or weak bases

• can exist in the ______ and/or __________ form, depending on the pH of the medium

pH of the Medium

IONIZATION:

• the acidity of the medium

Ionized

more polar = dissolves in aq.

Nonionized

nonpolar = passes the membrane

Positive or Negative

You will ionize the molecules - “you will free” their ions, either?

Polar

Making it more ____ → it will be excreted (“like disolves like”)

Therapeutic Effects

IONIZATION:

• If you have a weak acid drug product and you will subject it to an acidic environment, since “like absorbs like” = it will be absorbed. And vice versa

• If you subject a product to the same product, ionization will be cancelled, and there will be no ionization that will happen, which means the drug will be ________ and will produce?

Polar

IONIZATION:

• If you have a weak acid drug and subject it to a basic environment, ionization will happen, which is why you will have a more ______ drug product that is readily excreted.

Polar

IONIZATION:

• If you subject a weak basic drug to an acidic environment, it will be ionized, and since it is ionized, you will have a more ______ drug, which is readily excreted

Solubility

________ of the drug is a fundamental physicochemical property, and its dissolution is a fundamental physicochemical process