Spring and parachute

FIGURE 49.4 Spring and parachute performance of amorphous dispersions in comparison to crystalline material. 

Figure 3.4 Spring and parachute approach to promote and maintain supersaturation of celecoxib in solution. A high energy form of the drug (the spring) provides the driving force to solubilize the drug at a concentration greater than its equilibrium solubility level. / combination of excipients (the parachute) inhibits and/or retards precipitation...

A co-crystal of celecoxib with nicotinamide (Vitamin B3) was identified [49]. The co-crystal has a 1 1 stoichiometry and is comprised of hydrogen bonded nicotinamide dimers that sit within channels formed by celecoxib molecules, as elucidated by powder diffraction structure determination (Figure 3.5). The form rapidly dissociates when dispersed in aqueous solutions and the parent, celecoxib, precipitates in one of several forms depending on the excipients present. Although complex, the dissolution behaviour of the co-crystal has been evaluated and through the use of a spring and parachute approach, the in vitro performance of celecoxib nicotinamide was shown to be superior to that of the parent compound. 

Step 1 SPADS dissolution assay. Dissolution profile of an amorphous film is measured to assess the spring and parachute effect (Guzman et al. 2007). Selected polymer and drug loading set of ASD that meets the preset dissolution criteria... 

In order to explain the notable dissolution enhancement achieved by the dispersion of a poorly soluble drug into a hydrophilic polymer matrix, the spring and parachute model (Figure 5.3) has been proposed [17,24]. According to this model, the metastable... 

Figure 5.3 Schematic representation of the spring and parachute model high supersaturation relevant to the stable form of the drug is achieved by the use of the amorphous phase (the spring), while desupersaturation is retarded when favorable interactions with the hydrophilic polymer inhibit crystallization or facilitate the growth of metastable forms (the parachute). Reprinted with permission from [24], Copyright 2007 WUey.

When the bomb is released from the cluster, the arming bar springs away from the parachute opening delay, and the firing pin in... 

Fig. 2.12 Schematic showing of theoretical solution time profiles of a crystalline drug (black, dashed) and b pure amorphous drag without polymer (black), and solid dispersion with two different polymers A (medium gray) and B (light gray). Note that aU three amorphous formulations have a spring effect, while the polymer A exerts a parachute effect while polymer B completely inhibits recrystaUization and maintains the same degree of supersaturation...

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