[DDS-Lec] Liquid Forms

PART 1

• Solution

• Dispersed Systems

2 General Classes of Liquid Dosage form

• Emulsion

• Suspensions

Dispersed systems include

Solution

Liquid preparations that contain one or more chemical substances dissolved in a suitable solvent or mixture of two mutually miscible liquids.

Homogenous one-phase system consisting of two or more components

A solution is a?

Solution

Is the most commonly used liquid dosage form? It is a homogenous molecular mixture of two or more components

• Solute

• Solvent

Solute dissolved in a solvent

The simplest solution contains two components, what are they?

Can be in:

• Solid State

• Liquid State

• Gaseous State

The solute and solvent can be in what phase of matter?

1. solid solutes

2. liquid solvent

Most commonly, Pharmaceutical solutions are preparations in which the ______ such as excipients are dissolves in a _______ systems

• Use/Route of administration

• Composition

Types of solutions are based on

• Oral solution

• Otic solution

• Opthalmic solution

• Topical solution

Types of uses for solution

• Aqueous solution

• Non-aqueous solution

• Sterile solution

Types of composition for solutions

1. Completely homogenous doses

2. Immediate availability for absorption and distribution

3. Provides flexible dosage form

Advantages of solutions

• Easy to swallow

• Easy to adjust

• Can be used by any route of administration

Solutions provide flexible dosage forms which are:

• Solubility characteristics 

• Proper solvent

• Salt form

General rule in preparing solution:

Attractive forces

• What leads to the formation of molecule and ions that affects solubility

• This forces, which are developed between like molecules (such as H2O) are responsible for the physical state (Solid, Liquid, Gas) of the substances under given conditions.

the greater the solubility of the solute to the solvent.

The stronger the molecular forces between the solute molecule and solvent molecule, The ___________?

• Dipole-dipole (Van der Waals forces)

• Ion-dipole interaction

• Hydrogen bonding

Intermolecular Forces of Attraction (enumerate)

Dipole Dipole (Van der Waals forces)

Interaction where the negative pole of one molecule points towards the positive pole of the other

Ion-dipole interaction

Results of an electrostatic interaction between a charged ion and a molecule that has a dipole

Ion-dipole interaction

It is an attractive force that is commonly found in solutions, especially ionic compounds dissolved in polar liquids

Hydrogen Bonding

Involves strongly electronegative atoms such as oxygen, nitrogen and fluorine

• Oxygen

• Nitrogen

• Fluorine

Enumerate the strongly electronegative atoms

• Attractive forces

• Repulsive forces

When molecules interacts, what are in effect?

Breaking the solute-solute forces and the solvent-solvent forces

What is needed to achieve the solute-solvent attraction?

Solubility

• State when the total amount of solute in the solution and excess particles reaches equilibrium.

• As grams of solute dissolving in milliliters of solvent

Very soluble

<1

Freely soluble

1-10

Soluble

10-30

Sparingly soluble

30-100

Slightly soluble

100-1000

Very slightly soluble

1000-10,000

Practically insoluble or insoluble

>10,000

• Alcohol, USP

• Glycerin, USP

• Propylene glycol, USP

• Purified water, USP

Solvents for liquid preparation (enumerate)

• Ethyl alcohol

• Ethanol

Alcohol, USP is also known as

Alcohol, USP

Most useful solvent in pharmacy thus recognized as a solvent and excipient in the formulation of oral pharmaceutical products

• 64.9%-96% ethanol v/v at 15.56 C

• 99.5% (Dehydrated alcohol)

Properties of Alcohol USP (Enumerate)

volume in volume

v/v means?

Alcohol, USP

what is used as a primary solvent for organic compounds?

Dehydrated alcohol

Water free alcohol?

• Miscibility with water

• Ability to dissolve many water-soluble ingredients

• Used with other solvent(such as Glycol and Glycerin) that allows reduction of the amount of alcohol required

• Used as antimicrobial preservative alone (or with parabens)

Advantages of using Alcohol, USP

• Undesired pharmacologic effect

• Potential toxic effect

Disadvantages of using Alcohol, USP

0.5%

Alcohol content limit for children under 6 years of age

5%

Alcohol content limit for children at age 6-12 years of age

10%

Alcohol content limit for children over 12 years of age and adults

• Diluted alcohol, NF

• Rubbing alcohol

• Isopropyl alcohol

Types of alcohol preparations

70%

Rubbing alcohol contains about _____ ethyl alcohol

• 70% ethyl alcohol

• Water

• Denaturant (With or without color additives and perfume oils)

• Stabilizers

Rubbing alcohol contains

Diluted alcohol, NF

Mixture of alcohol, USP and Purified, USP

• Alcohol, USP

• Purified water, USP

Diluted alcohol is a mixture of?

the sum of two individual components

The final volume mixture of diluted alcohol is not _______

3% off or less than expected

The final volume of Diluted alcohol, NF is

49%

Concentration for diluted alcohol, NF

Diluted Alcohol, NF

Is a hydroalcoholic solvent in various pharmaceutical processes and preparations

Rubbing Alcohol

Contains about 70% ethyl alcohol or isopropyl alcohol by volume and the remainder consisting of water, denaturants and stabilizers

(Alcohol Rubbing Compound)

Rubbing alcohol is also known as

• 355 mg sucrose octa-acetate or 1.4 mg denatonium benzoate

• Bitter substances

Formulation of Rubbing Alcohol?

Discourages accidental oral ingestion or abusive oral ingestion

Purpose of bitter substances in rubbing alcohol

Formula 23-H

Denaturant agent employed in Rubbing alcohol

• Acetone (8 parts by volume)

• Methyl isobutyl ketone (1.5 parts by volume)

• Ethyl alcohol (100 parts by volume)

Composition of Formula 23-H

1. Discourage the illegal removal for use as a beverage of the alcoholic content.

2. Impossible separation of ethyl alcohol from the denaturants with ordinary distillation apparatus

Purpose of Formula 23-H:

Glycerol

Glycerin, USP is also known as

Glycerin, USP

Characteristics

1. Clear syrupy liquid with a sweet taste

2. Miscible wit water and alcohol

• Stabilizer

• Auxiliary solvent in conjunction with water and alcohol

What are the uses of Glycerin, USP?

Preservative qualities

Glycerin also has what qualities?

Propylene Glycol, USP

Characteristics:

• Viscous liquid

• Miscible with water and alcohol

• Solvent

• Substitute for Glycerin in pharmaceutical formulations

What are the use of Propylene Glycol, USP

Purified water, USP

most commonly used solvent for drug solution

• distillation

• ion exchange

• reverse osmosis

how is purified water obtained?

It has a fewer solid impurities than ordinary drinking water

Characteristics of purified water

0.001% of residues (1 mg of solid per 100 ml of water)

Solid impurities to purified water ratio

Purified water, USP

Solvent for preparations of aqueous dosage form except for those intended for parenteral preparations

• Water for injection, USP

• Bacteriostatic water for injection, USP

• Sterile water for injection, USP

• Sterile water for inhalation, USP

• Sterile water for irrigation

• Purified Water

USP recognizes 6 types of water for the use and preparations of dosage form

Purified water

Used for the preparation of medicines that do not have to be sterile and apyrogenic.

Highly purified water

Used for the preparation of medicines where water of high biological quality is needed, except where water for injection is required.

Water for injections

Used for medicines for parenteral administration. must be pyrogen-free

Sterilized water for injections

Used for medicines for parenteral administration. water has been sterilized by heat and is suitably packaged

• distillation method

• Ion-exchange method

• Reverse osmosis

Methods in preparing purified water

Distilled water

Distillation apparatus in distillation method yields what?

Deionized water

Ion-exchange equipment in ion-exchange method yields what?

Reverse osmosis

Is a cross-flow or tangential flow membrane filtration

Refer to Liquid dosage form PT 1: 19:48

DISCUSSION OF DISTILLATION PROCESS

10-20%

First portion of aqueous distillate in a distillation apparatus about ____ to ____ % must be discarded because it contains many foreign volatile substances

Distillation to dryness will result in decomposition of solid impurities to volatile substance that would distill and contaminate the collected portion of distillate

Last portion of water remaining in distillation apparatus must be discarded and not subjected to further distillation because??

Ion-Exchange method

Passes water through a column of cation and anion exchangers consisting of water-insoluble synthetic polymerized phenolic, carboxylic, amino or sulfonated resins.

• Cation or Acid exchangers

• Anion or Base exchangers

Two types of resins in ion-exchange method

Cations or acid exchangers

Permits the exchange of cations in solution with hydrogen ion

Anions or base exchangers

are resins which permit the removal of anions

• Elimination of heat

• Permit ease of operation

• Minimal maintenance

• More mobile facility

Advantages of Ion-exchange methods

Ion-Exchange method

Who is more advantageous between ion-exchange method and distillation method?

Reverse osmosis

Pressurized stream of water is passed parallel to the inner side of a filter membrane core.

Permeate

Filtered portion of reverse osmosis is called?

Concentrate

It contains the concentrated contaminate rejected by the membrane

Reverse osmosis

he flow through semi-permeable membrane is from high concentration to less concentration

Osmosis

The flow through semi-permeable membrane is from less concentration to more concentrated solution

• Microfiltration (0.1 to 2 μm) - bacteria

• Ultrafiltration (0.01-0.1 μm) - Virus

• Nano-filtration (0.001-0.01 μm) - Organic compounds in the MW of 300-1000

• Reverse osmosis - (<0.001μm)

Cross-flow membranes can remove particles defined in the range of:

1. Simple solutions

2. Chemical reaction

3. Solution by extraction

3 general methods for preparations of solutions

Simple solutions

Prepared by dissolving the solute in most of the solvent, mixing until dissolved then adding sufficient solvent to bring the solution up to the proper volume

Chemical reaction

Prepared by reacting two or more solutes with each other in a suitable solvent