Kinetics and Stability Studies III

Question 1

What is the goal for the development of any modified release formulation?

Answer 1

To:
i. enhance the drug’s therapeutic benefits
ii. minimize side-effects
iii. improve the overall management of the disease.

Question 2

Mention 3 types of drug release products.

Answer 2

i. Immediate release (Conventional release)
ii. Extended release (Modified release)
iii. Delayed release (Modified release)

Question 3

What are immediate release products?

Answer 3

They are oral dosage forms that rapidly release their API after administration and are subsequently absorbed into the blood stream from the GIT.

The plasma concentration of the drug peaks shortly after administration as absorption process dominates, then decreases over time as metabolism and/or excretion processes dominate.

[Mind the diagrams]

Question 4

What are extended-release products?

Answer 4

Also called extended-release, sustained-release and slow-release, these are oral dosage forms where the API is slowly released over an extended period of time.
They have a slower onset of action and a longer duration of action, and maintain therapeutic blood levels of a drug for a prolonged period.

Question 5

What do you understand by “controlled-release”?

Answer 5

The term “controlled-release” is a more specific term and may be defined as delivery of a drug at a predetermined rate for a defined time period.

Question 6

What do you understand by repeat action?

Answer 6

They are extended-release drug forms that usually contain two single doses of medication: one for immediate release and the second for delayed release.

Question 7

What are delayed release products?

Answer 7

Delayed-release dosage forms are defined as dosage forms that release a drug (or drugs) at a time other than promptly after administration.
DR technologies exhibit a lag time in drug release (no drug released immediately) to target the drug to a specific site in the body.

Question 8

What are the 5 mechanisms of release of controlled-release systems?

Answer 8

1. Diffusion-controlled release systems
2. Dissolution-controlled release systems
3. Dissolution and Diffusion controlled Release Systems
4. Ion exchange controlled release systems
5. Osmotic pressure controlled release systems

Question 9

Explain Diffusion-controlled release systems.

Answer 9

They rely on diffusion as the primary mechanism for drug release.
They are categorised into two main designs: reservoir and matrix systems, namely:

i) Reservoir systems: Drugs are trapped within an inert, water-insoluble polymeric membrane through which the drug molecules diffuse and release into the surrounding environment.

ii) Matrix systems: Drugs are uniformly dissolved throughout a polymeric matrix. As the matrix swells or degrades, the drug molecules diffuse out.

Question 10

Explain Dissolution-controlled release systems.

Answer 10

They involve the gradual release of drugs from slowly-dissolving polymeric carriers. They are of two main designs:

i) Reservoir Systems: drugs are encapsulated within slowly dissolving polymeric membranes. These membranes have low solubility, protecting the drugs and allowing controlled release

ii) Matrix/Monolithic Systems: drugs are embedded in a monolithic polymeric matrix. As the matrix dissolves, the drug is released.

Question 11

Explain Dissolution and Diffusion controlled release systems.

Answer 11

Drugs are trapped in partly soluble polymeric membranes or matrices that will dissolve to create pores.
Either one mechanism or a combination of both can occur during the release process. However, one may be dominant over the other.
The rate-limiting steps are:
- Diffusivity of drug
- Partition coefficient of drug
- Solubility of drug and polymers.

Question 12

Explain Ion exchange controlled release systems.

Answer 12

A solution of a cationic drug may be passed through a column containing an ion-exchange resin, forming a drug-resin complex, which is then washed and formulated into a capsule, tablet or suspension.

Question 13

Explain Osmotic pressure controlled release systems

Answer 13

The core drug is surrounded by a semi-permeable membrane coating with a 0.4 mm hole. As water is absorbed through the semipermeable membrane via osmosis, it creates osmotic pressure which pushes the drug through the hole.
[Mind the diagram]

Question 14

Mention 5 factors affecting physical stability of pharmaceutical dosage Forms

Answer 14

1. Colour change
2. pH
3. Odour
4. Texture
5. Turbidity

Question 15

Give an example of colour change as a factor affecting physical stability of pharmaceutical dosage forms.

What are preventive measures that should be taken?

Answer 15

• Ascorbic acid tablet turns yellowish brown
  -Adrenaline on exposure to air becomes red.

Preventive measures: The product should be protected from light and air.

Question 16

What are preventive measures that should be taken against pH change as an effect of degradation of pharmaceuticals.

Answer 16

Preventive measures : Addition of a water miscible solvent that will impact lower polarity.
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.

Question 17

Give an example of odour as a factor affecting physical stability of pharmaceutical dosage forms.

What are preventive measures that should be taken?

Answer 17

• Hydrolysis of aspirin produces acetic acid which
  gives off a smell of vinegar.

Preventive measures: Appropriate storage conditions of temperature and humidity.

Question 18

Give an example of texture change as a factor affecting physical stability of pharmaceutical dosage forms.

What are preventive measures that should be taken?

Answer 18

• Inappropriate viscosity of liquid preparations and abnormal feel of solid preparations.

Preventive measures: Appropriate storage conditions of temperature and humidity.

Question 19

Give an example of turbidity as a factor affecting physical stability of pharmaceutical dosage forms.

What are preventive measures that should be taken?

Answer 19

• Cloudy liquid preparations due to microbial growth.

Preventive measures: The pharmaceutical premise should be GMP compliant; therefore the production sites should be of positive air pressure.