**3. Techniques for manufacturing of ODTs**

The Orally disintegrating tablets could be prepared using various techniques such as direct compression, lyophilization, sublimation, tablet molding, and spray drying [34, 35].

#### **3.1 Direct compression**

Direct compression is a simple, cost-effective solution to produce robust tablets that retain the appropriate disintegration properties. It also provides better stability of active pharmaceutical ingredients, fast dissolution, simple validation, and low microbial contamination. Moreover, ODDTs manufactured via direct compression tend to have a much higher drug-loading capacity and the final mass of these ODTs easily exceeds that of other formulation techniques. On the other hand, tablets produced via direct compression have much higher physical resistance but take longer to disintegrate [36]. The basic principle of direct compression involves combining disintegrants, or effervescent agents, and hydrophilic ingredients. Superdisintegrants incorporated in optimum concentrations are often used to achieve rapid disintegration of ODDTs, as well as a good mouth feel [37]. Crospovidone is the disintegrants of choice for fastest disintegration, shortest wetting time, enhanced rate of drug dissolution, and robust tablets. This is because it swells without forming gels which can slow tablet disintegration or dissolution. But, other superdisintegrants form gels when fully hydrated, particularly when a high amount is used some formulations to achieve desired tablet disintegration or drug dissolution [38]*.*

#### **3.2 Freeze drying**

Freeze drying (lyophilization) is a process of removing water from a substance at lower temperatures under controlled conditions through sublimation [36]. This method has the advantage of allowing pharmaceutical compounds to be processed at lower temperatures, reducing sensitivity to thermal impacts, and allowing the solid to be kept in a dry environment with fewer stability issues. Because the resulting structures are relatively porous, lyophilization yields products that disintegrate more quickly than other solid dosage forms. Furthermore, the freeze-drying procedure causes the bulking agents in a formulation to have a glassy amorphous structure, which improves their disintegration capabilities. This approach produces ODTs with low mechanical strength that requires special packaging [26].

#### **3.3 Sublimation**

This method entails adding volatile chemicals such as ammonium bicarbonate, urea, naphthalene, and camphor to the other tablet ingredients before compressing them to make ODTs. Sublimation removes the volatile material trapped within the compressed tablets, resulting in the creation of pores within the formulation [22, 23, 39]. A high

porosity while used for the enhancing disintegration rate of ODTs is undesirable for tablet mechanical strength [40]. Because many ODTs are porous, if the processing parameters are not optimal, the tablets can become more friable, regardless of hardness adjustments. Co-processed excipients must be employed to make mechanically hard ODTs without sacrificing disintegration time [23, 41].
