**3. Drug stability**

The stability of a pharmaceutical product is defined as the capability of the product, in a specific container, to retain its efficacy, properties and characteristics throughout its shelf-life [4]. The recommended shelf-life (expiry date) for a commercial pharmaceutical product is 3–5 years. During this time, the concentration of the drug should not be reduced more than 95% of its value when originally prepared [5].

There are five types of stability that concern the pharmacist in the manufacturing of drugs:


**25**

*Drug Analysis*

*DOI: http://dx.doi.org/10.5772/intechopen.88739*

dosage regimen.

excipients [6, 7].

and identity).

*3.1.1 Hydrolysis (or solvolysis)*

allow hydrolysis of the drug [8].

*3.1.2 Ester hydrolysis*

(slope = +1) (**Figure 1**) [5].

*3.1.3 Amide hydrolysis*

hydrolysis [6].

active drugs with their solvent present (not water).

reaction involving acyl-oxygen cleavage. Ester hydrolysis is (H<sup>+</sup>

d.Therapeutic: the therapeutic effect remains unchanged within the specified

e.Toxicological: no significant increase in a predetermined toxicity effect is noted.

Stability types (therapeutic, microbiological, and toxicological) are basically

A stable drug is of great concern to the pharmacist (in view of marketing, storage and distribution); to the physician and patient (in view of safety and efficacy); and to the regulator and quality control analyst (in view of quality, strength, purity

Many drugs are derivatives of carboxylic acid or contain functional groups based on this moiety, for example esters, amides, lactones, lactams, imides or carbamates [5]. Accordingly, various chemical reactions can result in the degradation of the drug. These reactions include hydrolysis, oxidation, photochemical reactions, polymerization, isomerization, racemization and dehydration [4, 5, 8].

Hydrolysis forms the most common pathway by which drugs become degraded since many drugs contain hydrolysable functional groups. It can be defined as the process by which drug molecules interact with water to yield breakdown products of different chemical constitution. Hydrolysis occurs more readily in liquid state than in the solid state. It may occur in aqueous suspensions of sparingly soluble drugs. In tablets and other solid dosage forms, there may be sufficient water to

Solvolysis is a term used for the reactions involving the decomposition of the

Hydrolysis of drugs with an ester functional group (e.g. procaine, atropine, etc.) forms one of the most common types of drug instability. It is usually a bimolecular

catalyzed and is dependent on the specific compound and the pH of the solution. Atropine hydrolysis is totally pH dependent and this was characterized by the slopes of −1 and +1. In some cases, the hydrolysis of the drug can show a pH-profile with three regions: a hydrogen ion (proton) catalyzed region, (slope = −1), an uncatalyzed region (solvent dependent, slope = 0) and a hydroxyl ion-catalyzed region

Amides are generally more stable to hydrolysis than esters. In general the rate of hydroxyl ion-catalyzed reaction of amides is greater than the proton-catalyzed

) or (OH<sup>−</sup>) ion

Knowledge of the chemical stability of a drug is of great concern for selecting suitable storage condition against the effects of light, temperature, humidity, etc. and for anticipation of drugs interaction with each other or with

dependent on the chemical and physical properties of the drug.

**3.1 Chemical reactions that cause drug degradation**

*Pharmaceutical Formulation Design - Recent Practices*

bulk form or in a formulation.

pharmaceutical analysis should be capable of:

tion within acceptable stated limits.

chemical or photochemical causes).

specifications set by official standards.

substance (limit test application).

standards or monograph.

**3. Drug stability**

prepared [5].

ing of drugs:

and potency.

Pharmaceutical analysis can be divided into two types of methods:

a.Qualitative methods: these methods usually are used to ascertain the presence or identity of a component and\or impurities (predicted or expected).

b.Quantitative methods: determine how much of known drugs are present in

Since the judgment for quality of a drug depends on the method of analysis used, the validity or control of the method used is required. The methods used in

a.Correct identification of the drug in bulk form or as a formulated product.

b.Indicating the percentage of the stated content of a drug present in formula-

c.Indicating the stability of the drug in the formulation and hence the shelf life i.e. indicating the presence of a drug in its intact form and or the presence of any impurities (whether as drug precursors, decomposition products due to

d.Application in the dissolution rate studies i.e. at what rate is the drug released from its formulation so that can be absorbed by the body (bioavailability studies).

e.Ensuring that the identity and purity of pure drug (bulk form) meet official

f. Ensuring that the identity and purity of excipients used in formulation meet

g.Indicating the concentration of the specified impurities in the pure drug

The stability of a pharmaceutical product is defined as the capability of the product, in a specific container, to retain its efficacy, properties and characteristics throughout its shelf-life [4]. The recommended shelf-life (expiry date) for a commercial pharmaceutical product is 3–5 years. During this time, the concentration of the drug should not be reduced more than 95% of its value when originally

There are five types of stability that concern the pharmacist in the manufactur-

a.Chemical (including photochemical): the product retains its chemical integrity

b.Physical: the conformity of the pharmaceutical product (color, appearance,

c.Microbiological: sterilized products should remain sterile (no pyrogenicity).

dissolution, etc.) does not change upon storage or handling.

**24**

d.Therapeutic: the therapeutic effect remains unchanged within the specified dosage regimen.

e.Toxicological: no significant increase in a predetermined toxicity effect is noted.

Stability types (therapeutic, microbiological, and toxicological) are basically dependent on the chemical and physical properties of the drug.

Knowledge of the chemical stability of a drug is of great concern for selecting suitable storage condition against the effects of light, temperature, humidity, etc. and for anticipation of drugs interaction with each other or with excipients [6, 7].

A stable drug is of great concern to the pharmacist (in view of marketing, storage and distribution); to the physician and patient (in view of safety and efficacy); and to the regulator and quality control analyst (in view of quality, strength, purity and identity).
