The crystallization of seven active pharmaceutical ingredients (APIs) (acetaminophen (AAP), carbamazepine (CBMZ), caffeine (CAF), phenylbutazone (PBZ), risperidone (RIS), clozapine base (CPB), and fenofibrate (FF)) was studied in the absence and presence of microcrystalline cellulose (MCC) which acted as a heterosurface. Two of the active pharmaceutical ingredients (APIs), namely, AAP and CBMZ, possess hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) functionalities, whereas the other five possess HBA functionality only. Density functional theory (DFT) and molecular dynamics calculations complemented the experimental study. The smallest nucleation rate enhancement was observed for CBMZ at 1.4 times, and the largest was observed for FF at 16 times. For all the APIs studied, the interfacial energy was similar for crystallizations performed in the presence and absence of the heterosurface. By contrast, the pre-exponential factor was larger by a factor of ca. 2 and more for crystallizations carried out in the presence of the heterosurface. Arising from this study, a model of heterogeneous crystallization was developed wherein two influencing factors were identified. The first involves the issue of hydrogen bond complementarity between heterosurface and API. Hence, a HBD rich heterosurface will provide a hydrogen-bond mediated option for API cluster formation that would otherwise not be specifically available in solution to APIs possessing HBAs only. The second factor identified is that the lifetime of the hydrogen bond made by an individual API molecule or small API cluster with the heterosurface is up to 1000 times longer than (i) the lifetime of API−API interactions in a solution phase, or (ii) the time required for an API molecule to add to a growing crystal. This lifetime effect arises from the greater stability of an adsorbed species, and this extended lifetime increases the probability that other molecules or small clusters of the API in solution will add to the already adsorbed or attached species, thus encouraging the heterogeneous route to crystallization.

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This study is based on the heterogeneous nucleation of active pharmaceutical ingredients (APIs) 2 in the presence of various excipients widely used in the pharmaceutical industry. Carbamazepine (CBMZ) was successfully crystallized in the presence of the following heterosurfaces: α/β-4 Lactose, β-D-Mannitol, microcrystalline cellulose and carboxymethyl cellulose. The successful 5 crystallization of CBMZ FIII in the presence of all the excipients was confirmed by powder X-6 ray diffraction and scanning electron microscopy, while CBMZ crystals apposition was 7 confirmed using in-situ SEM-Raman. A pronounced improvement in the dissolution of CBMZ 8 FIII was observed when crystallized in the presence of excipients when compared with CBMZ 9 FIII recrystallized using same conditions in the absence of the excipients. The isolated solids 10 could be simply tabletted by direction compression upon mixing with the desired amount of 11 disintegrant and lubricant. Hence employing this process could potentially streamline the 12 downstream process in pharmaceutical industries and also increase the throughput with reduced 13 cost. 14

Domain diagram for supersaturation needed for a given polymorph pair to select kinetically the metastable or stable forms.

The effect of solvent on salicylamide's crystal habit was investigated. It is deduced that ethyl acetate is adsorbed more strongly on the faces, the increased size of which, can explain the shape change.

Bioactive nanomaterials, namely, gallium oxyhydroxide GaO(OH), also surface-conjugated GaO(OH) with a giant sugar molecule β-cyclodextrin (CD), have been prepared through a simple wet chemical route such that the same could be suitably used in biomedical diagnostics as well as therapeutic applications. Several physical methods were used for their characterization: powder X-ray diffraction pattern of GaO(OH) NPs for their grain size determination, optical spectroscopic absorption (UV-vis and FT-IR), and fluorescence properties of these NPs to ascertain surface conjugation and also their wide band-gap properties. Besides these, morphological properties of these NPs were studied by transmission electron microscopic (TEM) investigation, justifying the elemental constitution through energy dispersive X-ray analysis (EDX). Further, biological cellular uptake of these nanoparticles have been demonstrated on cancerous HeLa cells and reported with total fetal effect after 72 h, with CD templated GaO(OH) nanoparticles, a fact that has not been reported so far.

The crystal growth of tolbutamide (Form IL) in different solvents has been investigated by isothermal seeded desupersaturation experiments at different temperatures (268–283 K). Experimental data have been evaluated using empirical power law equations and the mechanistic based models: Burton–Cabrera–Frank (BCF) and birth and spread (B + S). The estimated activation energies and growth exponents suggest surface integration controlled growth as confirmed separately by mass transfer analysis. From the B + S model, the estimated solid–liquid interfacial energies and the mean diffusion distances on the surface range are 1.23–1.90 mJ/m2 and 1–16 nm, respectively. The growth rate is strongly dependent on the solvent, decreasing in the order: acetonitrile > ethanol > ethyl acetate > n-propanol > toluene. The crystal growth becomes slower as the overall strength of the solute–solvent binding increases. This influence of the solvent corresponds very well with that found for nucleation of tolbutamide in the same solvents and further supports the hypothesis that desolvation is an important step in crystallization. The similarity in the influence of the solvent on the kinetics of nucleation and growth very strongly supports the hypothesis that the solvent–solute interactions play an important role in the kinetics of formation of crystalline phases.

The crystal growth kinetics of piracetam, fenofibrate, phenylbutazone, acetaminophen, carbamazepine, and risperidone in methanol have been studied by two different methods; the isothermal seeded desupersaturation experiment (ISD) and the rotating disk technique (RD). Data has been collected in the range of temperature 288−303 K and at different supersaturations for the ISD experiments. The RD experiments were performed at constant supersaturation. In the ISD experiments, principal component analysis has been used to relate solution concentrations from IR measurements. An empirical power law equation has been fitted to the experimental desupersaturation data, and parameter values suggest surface integration control for all the APIs studied, a conclusion further supported by a separate mass transfer analysis. The order of rate of growth among the compounds and the magnitude of the growth rates determined by the two methods are in good agreement. In addition, the Burton Cabrera Frank (BCF) and Birth and Spread (B+S) surface integration models have been fitted to the ISD desupersaturation data, and average solid−liquid interfacial energies, mean diffusion distances, and surface mass transport rates have been estimated. An analysis of the experimental results and the growth rate parameters is performed to examine to what extent the difference in growth rate of different compounds can be rationalized.