*3.1.3 Amide hydrolysis*

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 hydrolysis [6].

**Figure 1.** *Log rate*-*pH profile for the degradation of atropine at 60°C.*

Penicillins and cephalosporins are amides in which the amide bond is part of the strained four membered ß-lactam rings. Their decomposition is catalyzed by hydrogen ion, hydroxyl ion and many buffers. Therefore, these compounds are too unstable to be formulated as solutions. Their pH profile is generally similar to the pH-profile shown in **Figure 1**.

In addition to acid-base catalyzed hydrolysis, enzyme-catalyzed hydrolysis may take place in drugs of natural origin; for example enzymes catalyzes the hydrolysis of cardiac glycosides in digitalis leaf [8].

#### *3.1.4 Oxidation*

Oxidation involves the removal of an electropositive atom, radical or electron, or the addition of an electronegative atom or radical. When a reaction involves molecular oxygen (O▬O), it is commonly called autoxidation and this forms the most common pathway of oxidative decomposition of pharmaceuticals.

Oxidative degradation by autoxidation may involve chain processes consisting of three concurrent reactions—initiation, propagation and termination. Initiation can be via free radicals formed from organic compounds by the action of light, heat or transition metals such as copper and iron which are present in trace amounts in almost every buffer [5].

Many drugs are complex molecules and can be subjected to both hydrolysis and oxidation e.g. steroids, anti-inflammatory, polyene antibiotics (amphotericin B) etc.

**Figure 2** show the oxidation of phenothiazines to the sulfoxide which involves two single-electron transfer reactions involving a radical cation intermediate. The sulfoxide is subsequently formed by reaction of the cation with water [5].

Oxidation in solution generally follows first or second order kinetics. Some oxidation reactions are redox reactions that involve the loss of electrons without the addition of oxygen e.g. oxidation of ascorbic acid, ferrous sulfate, adrenaline and riboflavin [8].

In addition to oxidation and hydrolysis, many other degradative reactions had been studied including addition, dehydration, polymerization, isomerization, acylation, transesterification, etc.

**27**

**Figure 2.**

*3.1.5 Photochemical degradation*

*Phenothiazine oxidation process.*

These are the reactions that take place by absorption of the visible or ultraviolet light. The reactant molecule absorbs photons of light (energy) and get excited. The

In many photochemical reactions, the reactant molecule may not absorb the radiation directly but through a mediator which absorbs the incident radiation and subsequently transfers its energy to the reactant molecule that becomes activated.

At times, a molecule can act as a protector for the photolabile drug by preferentially absorbing the radiant energy and produce products. These compounds are

excited molecule then produces the photodecomposition product.

Such type of mediator is called photosensitizer.

referred to as screening agents [9].

*Drug Analysis*

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

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

*Pharmaceutical Formulation Design - Recent Practices*

pH-profile shown in **Figure 1**.

*3.1.4 Oxidation*

**Figure 1.**

pharmaceuticals.

almost every buffer [5].

of cardiac glycosides in digitalis leaf [8].

*Log rate*-*pH profile for the degradation of atropine at 60°C.*

Penicillins and cephalosporins are amides in which the amide bond is part of the strained four membered ß-lactam rings. Their decomposition is catalyzed by hydrogen ion, hydroxyl ion and many buffers. Therefore, these compounds are too unstable to be formulated as solutions. Their pH profile is generally similar to the

In addition to acid-base catalyzed hydrolysis, enzyme-catalyzed hydrolysis may take place in drugs of natural origin; for example enzymes catalyzes the hydrolysis

Oxidation involves the removal of an electropositive atom, radical or electron, or the addition of an electronegative atom or radical. When a reaction involves molecular oxygen (O▬O), it is commonly called autoxidation and this forms the most common pathway of oxidative decomposition of

Oxidative degradation by autoxidation may involve chain processes consisting of three concurrent reactions—initiation, propagation and termination. Initiation can be via free radicals formed from organic compounds by the action of light, heat or transition metals such as copper and iron which are present in trace amounts in

Many drugs are complex molecules and can be subjected to both hydrolysis and oxidation e.g. steroids, anti-inflammatory, polyene antibiotics (amphotericin B) etc. **Figure 2** show the oxidation of phenothiazines to the sulfoxide which involves two single-electron transfer reactions involving a radical cation intermediate. The

sulfoxide is subsequently formed by reaction of the cation with water [5].

Oxidation in solution generally follows first or second order kinetics. Some oxidation reactions are redox reactions that involve the loss of electrons without the addition of oxygen e.g. oxidation of ascorbic acid, ferrous sulfate, adrenaline and

In addition to oxidation and hydrolysis, many other degradative reactions had been studied including addition, dehydration, polymerization, isomerization,

**26**

riboflavin [8].

acylation, transesterification, etc.

**Figure 2.** *Phenothiazine oxidation process.*
