# Application of Polymers as a Tool in Crystallization--A Review
## 2 Basic Research
### Discussion and Conclusions
#### 3.2.1 Antinflammatory Drugs  
Polymers can be applied in both directions--preventing the nucleation/precipitation as well as for direct control of the crystallization/precipitation processes. [PERSON] and [PERSON] showed that PVP-induced crystallization of celecoxib (nonsteroidal anti-inflammatory drug) improved its bioavailability, stability and processability [55]. Celecoxib as a model drug was also used in experiments presented by [PERSON] et al. Using the microarray plate method they tested the inhibition performance of HPC, HPMC and PVP on the crystallization of celecoxib [56]. The applicability of the microarray plate method for quantitative estimation of precipitation kinetics for poorly soluble drugs was demonstrated. [PERSON] and [PERSON] reported the results of a simulation showing that paracetamol aggregation is predominantly governed by the size of the pores of poly(ethylene glycol diacrylate) and the polymer-paracetamol interactions play a secondary role [57]. [PERSON] et al. described the experiments in which the tailor-made copolymers of \(N\)-hydroxyphenyl methacrylate and styrene decreased the induction time for paracetamol crystals appearance [58]. In their paper [PERSON] et al. proposed a new method of inducing the preferred mono- or ortholomorphic forms of paracetamol through the swift cooling of boiled aqueous solution in the presence of selective polymers such as nylon 6/6 (C\({}_{12}\)H\({}_{22}\)N\({}_{2}\)O\({}_{2}\))\({}_{h}\), polypropylene (C\({}_{3}\)H\({}_{6}\))\({}_{n}\) and polyvinylchloride (C\({}_{2}\)H\({}_{3}\)Cl)\({}_{n}\)[59]. [PERSON] et al. investigated the polymer-induced heteronucleation method to test the effect of nylon 66, PET and polypropylene films on the crystal growth of paracetamol and found different induction times for different polymers [60]. [PERSON] et al. utilized biocompatible 2-hydroxyethyl cellulose thin films to enhance the nucleation rates of paracetamol and found that flat polymer films without nano-imprinting enabled the crystallization of paracetamol two times faster than bulk crystallization [61]. [PERSON] and [PERSON] reported a methodology for comparing nucleation efficiencies of different functionalities on polymer heteronuclei of uniform topology (functionalized cross-linked poly(chloromethylstyrene)) that best accelerate nucleation of paracetamol [62]. The presented study shows that the increased hydrophobicity of the resin functionalized with methylated paracetamol results in faster heteronucleation of the drug, as evidenced by its higher average induction time. [PERSON] et al. reported the methodology to control crystal polymorphism through the use of diverse polymer heteronucleic including both commercially available and synthesized cross-linked polymers [63]. The proposed technique was successfully demonstrated in pharmaceuticals such as paracetamol, sulfamethoxazole (an antibiotic used against bacterial infections) and carbamazepine (an anticonvulsant drug). This new approach offers the advantage of producing multiple polymorphs. [PERSON] et al. demonstrated a new approach for designing and fabricating biocompatible PVA films that can enhance nucleation rates and enabled polymorph selection of small-molecule compounds such as aspirin (medication used to reduce pain, fever, and inflammation) and indomethacin [64]. The research shows that PVA accelerated the heterogeneous nucleation rates of drugs. [PERSON] et al. tested three different polymers, i.e., PVP, HPMC, and Kollidone, to assess their impact on the nucleation and crystal growth of indomethacin from supersaturation solutions [65]. [PERSON] et al. patterned polymer films based on PAA crosslinked with DVB with nanopores of various shapes and found that spherical nanopores 15-120 nm in diameter hindered the nucleation of aspirin crystals, whereas angular nanopores of the same size promoted it [66]. Their results can be used in the control of pharmaceutical polymorphism and for the regulation of the crystallization of fine chemicals. They used aspirin and indomethacin as model compounds.