- Ceutics - mona

- Factors affecting drug stability – shadi

- Drug factors for passage into the breast milk - shadi
- Solution types
- Notes
- MCQs
- USP sterilization – saif
- Compounding sterile preparation – shadi
 Ceutics
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Drug Cross

Absorption in stomach
-

non-ionized

non-polar

Lipid soluble

Cross BBB
-

Unionized

Lipophilic

Cross the placenta

-

Mwt < 500

Lipophilic

Non-ionized

Ceutics 1
 # Protein bound NOT cross PlacentaONLY the free unbound

Metabolism Drug Additive

After metabolism Drug become: Polar →
polar
Drug Additive
After metabolism

- -

ISO classification
ISO classification of particulate matter in room air

Ceutics 2
3-
8 ( my

d
"

USP General Chapters

Ceutics 3
 :
:-.
Route of drug administration

Ceutics 4
 ✓
✓

r
✓

• -

✓ ✓

Ceutics 5
 i
-

Sterilization

Definition
Sterility may be defined as the total absence of viable microorganisms and is an
absolute state.
-
-

The production of sterile pharmaceutical products may be achieved by aseptic

technique (by means of a terminal steriliza tion process)
-

Methods

1- Steam

Definition
Autoclave and employs steam under pressure.
bacterial cells with a large percentage of water are generally killed
-

-
rather easily. Spores, which contain a relatively low percentage of
-

water, are comparatively difficult to destroy

Ceutics 6
 Use for
With autoclave

:
(Surgical Instruments - Glassware - Plastic tubes and pipette tips -
Solutions and water)
With moist heat
(pasteurization - Sterilization of vaccines - Sterilization of serum and
body fluids)

2- Dry heat

Definition
Higher temperatures permit shorter exposure, The lethal effect is due to
the oxidation of microbial proteins.

-
generally employed for substances that are not effectively sterilized by
moist heat such as (fixed oils; glycerin; various petroleum products)
-

Techniques
Incineration
Hot-air oven
The infrared oven
The infrared vacuum oven

Use for
Glassware
Porcelain and metal articles
Oils and similar anhydrous materials
Powders
Paraffin gauze dressings

3- Filtration

Definition
Unlike other methods of sterilization, filtration works by removing
-

microorganisms rather than killing or destroying them

- -
se
Techniques

Ceutics 7
 If physical removal of microorganisms by:
1- Adsorption on the filter medium

of
-

2- A sieving mechanism, It is used for heat-sensitive solutions.

---

To remove microorganisms the filter must have a pore size of

approximately 0.2 μm. Larger pore sizes (e.g., 5 μm) are used to
_o -
I _@

remove particulate matter.

Bacteria
Vir sus
+

iron
.
.

Nickle
,

+
Hydrogen
U
Na .

Types of Dosage form

Ceutics 8
 Solubility

too
Solution
A solution is a homogeneous mixture consisting of a solute dissolved into a
solvent.

Solute
The solute is the substance that is being dissolved (‫)اﻟﺬاﺋﺐ‬

5-
And is the material present in the smaller amount in the solution.

Solvent
The solvent is the dissolving medium. (‫)اﻟﻤﺬﻳﺐ‬
And is the material present in the larger amount in the solution.

Solubility
Solubility is the relative ability of a solute to dissolve into a solvent.

Factors Affecting Solubility

Ceutics 9
 Temperature → Increase Solubility
Polarity → “Like dissolves like.” a solute will dissolve best in a solvent that
has a similar chemical structure

Part of solvent required per part of solute

Ceutics 10
 Types Of Tablet

Immediate-release tablets
Immediate-release tablets are designed to disin-tegrate and release their

£
medication with no special rate-controlling features.
-

Enteric-coated tablets
Have delayed-release features. They are designed to pass unchanged through
-

the stomach to the intestines, where the tablets disintegrate and allow drug
dissolution and absorption and/or effect. Enteric coatings are employed when

Ceutics 11
 -0
the drug substance is destroyed by gastric acid or is particularly irritating to the
-

gastric mucosao
-
or when bypass of the stomach substantially enhances drug
absorption.

Extended-release tablets
(sometimes called controlled-release tablets) are designedto release their
-

medication in a predetermined manner over an extended period

Buccal and sublingual tablets

Are flat, oval tab- lets intended to be dissolved in the buccal pouch (buccal
- -

tablets) or beneath the tongue (sublin- gual tablets) for absorption through the
-

oral mucosa. They enable oral absorption of drugs that are destroyed by the
•are poorly absorbed from the gastrointestinal tract.
gastric juice and/or
-

Chewable tablets
Which have a smooth, rapid disintegration when chewed or allowed to dis-
solve in the mouth, have a creamy base, usually of specially flavored and
=

colored mannitol
-

Effervescent tablets
Are prepared by compressing granular effervescent salts that release gas
mainly is CO2 carbon dioxide gas into liquid when it contact with water. These
tablets generally contain medicinal substances that dissolve rapidly when
added to water. The “bubble action” can assist in breaking up the tablets and
enhancing the dissolution of the active drug.

Vaginal tablets
-

Also called vaginal inserts, are uncoated, bullet-shaped or ovoid tablets inserted
-

-
into the vagina for local effects. They are pre- pared by compression and
shaped to fit snugly on plastic inserter devices that accompany the product.

Types of IV fluids

Ceutics 12
 swell shrink

- -

- -

_-
-

• •
-

-
-
fie

Ceutics 13
 -

E-
-

-
__ = -

Bicarb .

y
lactate

Ceutics 14
 a
%
o -

Nad → →
0:45 % -
DSW
%
-

☐ 20W
↳ 0 .
225

=
I
f-

•
•

Note

Ceutics 15
 Factors affecting drug stability
Temperature
High temperature accelerate oxidation, reduction and hydrolysis reaction which lead to drug degradation
pH
• Acidic and alkaline pH influence the rate of decomposition of most drugs.
• Many drugs are stable between pH 4 and 8.
• Weekly acidic and basic drugs show good solubility when they are ionized and they also decompose
faster when they are ionized.
• So if the pH of a drug solution has to be adjusted to improve solubility and the resultant pH leads to
instability then a way out of this tricky problem is to introduce a water miscible solvent into the product. It
will increase stability by:
- suppressing ionization
- reducing the extreme pH required to achieve solubility
- enhancing solubility and
- reducing the water activity by reducing the polarity of the solvent. For example, 20% propylene glycol is
placed in chlordiazepoxide injection for this purpose.
Moisture
a. Water catalyses chemical reactions as oxidation, hydrolysis and reduction reaction
b. Water promotes microbial growth
Light
Affects drug stability through its energy or thermal effect which lead to oxidation
Pharmaceutical dosage forms:
Solid dosage forms are more stable than liquid dosage forms for presence of water.
Concentration
Rate of drug degradation is constant for the solutions of the same drug with different concentration.
So, ratio of degraded part to total amount of drug in diluted solution is bigger than of concentrated
solution.
Stock solutions: are concentrated solutions which diluted by using (i.e. syrup 85%) at high concentration
the stability is high
Drug incompatibility
Reactions between components of pharmaceutical dosage forms it self or between these components and
cover of the container .
Oxygen
Exposure of drug formulations to oxygen affects their stability
 .Drug factors for passage into the breast milk
Molecular weight -1
Drugs weighing 200 Da cross into milk easily. Larger molecules can dissolve in the lipid membrane or pass through
.small pores. Large molecules, such as insulin, do not cross into breast milk
pH gradient .2
.Human milk is more acidic than plasma
a. Weak acids may diff use across the membrane and remain un-ionized, allowing for passage back into the plasma.
.Lower amounts of these drugs will cross than those that are weak bases
b. Weak bases may diff use into the breast milk and ionize, which causes drug trapping. This creates higher levels of
.drug in the breast milk; these drugs will have a milk to plasma ratio > 1
This effect though is not usually clinically significant, especially when the maternal serum concentration is very low
.Drug pKa .3
.Only the un-ionized form of a drug is able to pass through the lipid membrane

.Plasma protein binding .4

The free fraction of a drug is available to pass into the breast milk. In general, drugs with high
plasma-protein-binding properties tend to remain in the plasma and pass into the milk in low concentrations. Milk
proteins and lipids also may bind drugs when they are created in the mammary glands; this may represent another
.route of entry, rather than passive diffusion
.Lipid solubility .5
Lipid solubility is necessary for a drug to pass into the breast milk. Highly lipidsoluble drugs (e.g., diazepam
[Valium]) may pass into the breast milk in relatively high amounts and, therefore, may present a significant dose of
.drug to the nursing infant
.Equilibration .6
Some drugs may rapidly equilibrate between maternal plasma and breast milk. Th ese agents will diff use across the
membrane as the drug concentration changes in the maternal system. Other agents may never reach equilibrium
between milk and plasma. These drugs tend to slowly diff use into breast milk and will respond gradually to changes
.in maternal concentrations
 Preparation

Prepare emulsion: continental, dry gum method, wet gum method

Preparation can be use externally as optic waxes remover !:

Glycerin + 5% sodium bicarbonate

NOT prepared in horizontal laminar flow: large volume fluid

Not consider formation of suspension: use chelating agent

Boric acid in preparation: puffer

Agents:

Gums used in tableting as: Binding agent

Aspartame added to preparation as: sweeting agent
Bentonite used as: suspending agent and Rheological agent
Vit C in preparation: preservative
Used to prepare suppository: Cocoa butter
Oleaginous base: white petroleum
Which preparation have more moisture: ointment

Water:

Which type of water use in cold cream: Distilled water

Which type of water use in large amount of parental: sterile water for injection

Normal water used for preparation of: External preparation

# Pka for normal water in room temp: 14

Sterilization:

Method sterilization our society: Autoclave

Method used in sterilization: moist heat, dry heat

Methods:

Decoction: Extraction active material from plant by boiling 🔥 🌱

Liquid dissolved in liquid: Miscibility
Levigation: grinding an insoluble substance to fine powder (dec. size)
Tablet to powder: Disintegration
Freeze drying is done by: Sublimation
Big fragments into small fragments: Reduction

From more lipid to less lipid: Biotransformation

Grinding powder before adding it: Trituration

The most common disintegrator in compressed tablet is: Starch

Parameter describing dissociation in solution: Pka

Ophthalmic preparation should have 👁 : Sterile, Purified, Isotonic

PH of eye preparation 👁: 6-8

Surfactant use orally: Tween & Span

Surfactant NOT use orally: Na lauryl sulphate
 Pharmacutics

1 What process hinder drug from dissolution

Make tablet more compressed

2 Issues of large tablets

delay dissolution

3 What is the basis of pharmaceutics for drug classification?

solubility and partition coefficient

4 Which one prevent tablet dissolution?

Hard compressing tablets

5 grinding of solid or powder in liquid or ointment is ?

LEVIGATION

6 When we decrease particles size?

In limited dissolution substance

7 Drug with high Distribution Volume, What Means ?

conc. of drug in tissues is higher than that in plasma

8 A fixed dose of drug that follows 1" order elimination depends on ?

dose of drug

9 45 year old man his volume of distribution is 35 L what the interpretation ?

drug is highly distributed in.plasma

10 Plasma conc. Of drug in all body is ?

rate of distribution

11 PKa for normal water in room temperature ?

14

12 Characters of liquid dosage form

Fast in absorption

13 Aspirin Pka will be stable at PH 3.2

2

14 A fixed dose of drug that follows 1" order elimination depends on ?

dose of drug

15 Which is not considered in formation of suspension

Use chelating agent

16 Flavor used in drugs

Fruit

17 All factors affect the distribution of drugs except

type enzyme response from metabolism
18 45 year old man his volume of distribution is 35 L what the interpretation ?
drug is highly distributed in.plasma
 7/23/20

SAIF ALGHAMDI
‫توكلت على اهلل‬

1
Expire date= chemical stability
BUD= both chemical and microbial stability
Horizontal Flow Hoods: Non Chemotherapy’s - Air Exhausted grile
Vertical Flow Hoods: Chemotherapy’s medication - Hazard - Toxic
7/23/20
The pressure have to be positive except: in chemotherapy have to be negative
Iso class 100: Positive pressure

Hazard ISO 7

HEPA filter: 0.3 micron and more

✔ Membrane filter: 0.22 micron

ULPA filter: 0.12 micron

✔

ISO class 8: Anteroom - Transition

ISO class 7: Buffer area - supply and equipment used in CSP
ISO class 5: Primary engineering control - Extremely vented - HEPA - LAFH
Iso class 100: Isolators barrier - only one person can work here - Hazard drug 2
The pressure inside the clean room must: Greater than the outside room
Minimum Frequency for Cleaning of Specific Sites (Reprinted with Permission from USP Chapter 797
ISO Class 5 PEC Beginning of each shift Before each batch Every 30 minutes when
compounding After spills When surface contamination is known or
suspected
Counters and easily Daily
cleanable work surfaces
Floors Daily
Walls Monthly
Ceilings Monthly
Storage shelving Monthly

Controlled Temperatures (Data from USP General Notices and Requirements58)

Storage Condition Centigrade Fahrenheit
Room temperature 20 to 25 °C 68 to 77 °F
Cold temperature 2 to 8 °C 36 to 46 °F
(refrigerated)
Freezer (frozen) to 10 °C –13 to 14 °F

INTERNATIONAL ORGANIZATION OF STANDARDIZATION (ISO) CLASSIFICATION OF

PARTICULATE MATTER IN ROOM AIR
ISO Class ISO (Particles per cubic meter)
3 35.2
4 352
5 3,520
6 35,200
7 352,000
8 3,520,000
Terminal sterilization: cleaning at end of work - Thermostable produces ‫يتحمل الحرارة‬
Aseptic sterilization: The pharmacist use it in IV room as always - Thermoliable ‫ما يتحمل‬
 Low risk: Single sterile dosage
Medium risk: multiple sterile dosage
High risk: non sterile
Risk Level Classification
LOW This category encompasses simple admixtures involving closed-system transfer, measuring, and mixing of
three or fewer commercially manufactured sterile products (including the infusion solution). Low-risk
compounding conditions must include all of the following:
CSPs are compounded using aseptic technique within an ISO Class 5 PEC (e.g., LAFW, BSC, CAI, or
CACI) that is located within an ISO Class 7 buffer area with an ISO Class 8 ante area.
Each container, including the final container, may not be entered more than twice to prepare the CSP.
Compounding is limited to aseptic manipulations of disinfected containers using sterile needles and
syringes.
Medium This category encompasses preparations requiring more complex compounding processes, including:
Multiple doses of sterile products combined or pooled to prepare a product that will be administered
either to multiple patients (i.e., batching of syringes or large volumes), or one patient on multiple
occasions (e.g., preparation for use over several days).49
More than three commercially available sterile products are used to produce the compound.
More complex compounding processes (e.g., total parenteral nutrition).
All requirements for low-risk compounding regarding location and aseptic technique must be
followed
High High-risk CSPs are those
Prepared from nonsterile ingredients, including manufactured products not intended for sterile
routes of administration.
Compounded using a nonsterile device prior to terminal sterilization.
Containing nonsterile water that are stored for more than 6 hours before sterilization.
Exposed to conditions worse than ISO Class 5 air quality for longer than 1 hour, if they contain or are
compounded from sterile contents of commercially manufactured products or CSPs without
antimicrobial preservatives.
Containing bulk ingredients whose chemical purity and content strength are not verified by labeling
and documentation from suppliers or by direct determination.
Prepared by compounding personnel who are improperly garbed or gloved