Solvent Drop Grinding Method Research Articles

Co-crystallization of Hesperidin with different co-formers to enhance solubility, antioxidant and anti-inflammatory activities

Hesperidin (HSP) is a natural flavonoid glycoside with very low aqueous solubility and a slow dissolution rate, limiting its effectiveness. This study aims to address these issues by creating co-crystals of hesperidin with water-soluble small molecules (co-formers) such as L-arginine, glutathione, glycine, and nicotinamide. Using the solvent drop grinding method, we prepared three different molar ratios of hesperidin to co-formers (1:1, 1:3, and 1:5) and conducted in-vitro solubility and dissolution studies. The results demonstrated that the prepared co-crystals exhibited significantly enhanced solubility and dissolution rates compared to untreated hesperidin. Of particular note, the HSP co-crystals formula (HSP: L-arg 1:5) displayed approximately 4.5 times higher dissolution than pure hesperidin. Further analysis using FTIR, powder x-ray diffraction patterns, and DSC thermograms validated the formation of co-crystals between HSP and L-arginine. Additionally, co-crystallization with L-arginine improved the in vitro anti-inflammatory and antioxidant activities of hesperidin compared to the untreated drug. This study highlights the potential of using water-soluble small molecules (co-formers) through co-crystallization to enhance the solubility, dissolution, and biological activities of poorly water-soluble drugs. Furthermore, in vivo studies are crucial to validate these promising results.

Ketoprofen-Tromethamine: Binary Phase Diagram of Multicomponent Crystal, Dissolution Rate, and Analgesic Activity Evaluation

Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) whose formulation options are limited due to its low dissolution rate in aqueous media. This research aimed to enhance the solubility of ketoprofen in distilled water and to compare the anti-inflammatory and analgesic effects of its resulting multicomponent crystal with tromethamine. The binary phase diagram of ketoprofen-tromethamine was created across molar ratios ranging from 1:9 to 9:1. The multicomponent crystal comprising ketoprofen and tromethamine in the selected ratio was synthesized using a solvent drop grinding method and subjected to further characterization for thermal properties, crystallinity, chemical groups, and morphology. The dissolution rate assessments were evaluated in CO2-free distilled water. Pharmacological analyses examined the anti-inflammatory and analgesic effects of the multicomponent crystal. The binary phase analysis identified the 5:5 (1:1) molar ratio as optimal in forming a multicomponent crystal. Thermograms and diffractograms revealed crystalline alterations attributed to a new crystalline phase. The new multicomponent crystal exhibited approximately 2.7 times higher dissolution rate after 30 minutes, outperforming pure ketoprofen. Pharmacological assessments demonstrated superior analgesic effects of the multicomponent crystal. In summary, the ketoprofen-tromethamine cocrystal in 1:1 molar ratio offers enhanced dissolution rate and provides better analgesic activity than ketoprofen alone.

Preparation and Characterization of Multicomponent Crystal Piperine-Caffeine

Piperine (C17H19NO3) belongs to the alkaloid group mainly found in the Piperaceae family, especially in black pepper (Piper nigrum L.). Piperine is practically insoluble in water. This study aims to improve the solubility of piperine by preparing it into a multicomponent crystal using caffeine as a coformer. The formation of piperine-caffeine multicomponent was prepared by solvent evaporation and solvent drop grinding. Each sample was characterized using Powder X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and FT-IR spectroscopy. The solubility test was carried out by sonication for 30 minutes at room temperature (30 ⁰C), and the dissolved piperine was analyzed by High-Performance Liquid Chromatography (HPLC) using methanol: water (80:20) as the mobile phase. This study shows a decrease in peak diffraction intensity on PXRD analysis and a reduction in endothermic peak on the DSC thermogram of multicomponent crystals. In the FTIR analysis, multicomponent crystals slightly shift, indicating the physical interaction. The multicomponent crystal of piperine-caffeine prepared by solvent evaporation method has an increase in solubility of 2.56 times, and the multicomponent crystal with solvent drop grinding method has an increase in solubility of 1.61 times, respectively. In conclusion, the multicomponent crystal piperine–caffeine can enhance the solubility of piperine.

Solubility Enhancement of Clozapine by Co-crystals

Cocrystallization of drug with coformers is a promising approach to alter the solid state properties of drug substances like solubility and dissolution. The objective of the present work was preparation, formulation and evaluation of the clozapine cocrystal by screening various coformers. Clozapine co-crystals were prepared using different coformers like benzoic acid, fumaric acid, sodium saccharin and sodium acetate. Cocrystals were prepared using solvent evaporation method and solvent drop grinding method. The prepared co-crystals were evaluated for saturation solubility, drug content, dissolution studies, XRD studies and DSC analysis.

Comparative assessment of solubility enhancement of itroconazole by solid dispersion and co-crystallization technique: Investigation of simultaneous effect of media composition on drug dissolution

Solubility of the drug is an important property of the drug as it affects the release, absorption, dissolution rate and ultimately bioavailability of the drug. Hence, the poorly aqueous soluble drug, need to be processed, to enhance its solubility and dissolution. The Biopharmaceutical System of Classification (BCS) II drugs are poorly soluble and have high permeability. Though their good ability to permeate through the membrane make them clinically useful but the problem associated with the solubility restrict their clinical use. Therefore, there is need to improve the solubility of such drug molecules to get effective pharmacological action. Itraconazole (ITZ) is an antifungal agent used in the treatment of fungal infections having poor aqueous solubility as belonging to BCS class II. The present study was aim to enhance the solubility of ITZ by solid dispersion and co-crystallization techniques. Investigation of simultaneous effect of media composition on drug dissolution was also the objective of this work. The ITZ-SD and ITZ-CCs were prepared from ITZ and other excipients like PEG 4000, oxalic acid, fumaric and malic acid by solvent evaporation, kneading technique, slurry conversion and solvent drop grinding methods. The prepared ITZ-SD, ITZ-OA-CCs, ITZ-FA-CCs and ITZ-MA-CCs were evaluated for FTIR, DSC, PXRD, % yield, micromeritic properties. The optimized ITZ-SD and ITZ-CCs were used to compress a tablet and subject to post-compression parameters. The results of FTIR and DSC showed the absence of interaction between the drug and excipients. The PXRD pattern demonstrated the formation of crystalline structures with 6 folds increased in solubility during saturation solubility analysis. In vitro dissolution was carried out in dissolution media with different pH which shows the maximum release from ITZ-SD and ITZ-CCs in pH 6.8. This also revealed the highly pH dependent solubility and dissolution behavior of the weakly basic BCS class II drug (ITZ) with pKa value of 3.7. The overall results in this study indicated the potential of solid dispersion and co-crystals for enhancement of solubility of the poorly water-soluble drugs.

FORMATION AND CHARACTERIZATION OF MULTICOMPONENT CRYSTAL OF TRIMETHOPRIM AND MANDELIC ACID BY SOLVENT DROP GRINDING METHOD

Objective: To increase the solubility of trimethoprim by forming multicomponent crystals using mandelic acid as a coformer.
 Methods: Multicomponent crystals of trimethoprim and mandelic acid were prepared at a ratio of 1:1 mol by the Solvent Drop Grinding (SDG) method. Solid state characterization was carried out using Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscope (SEM), and polarized microscope. The solubility test of trimethoprim was carried out in CO2-free distilled water using a sonicator for 5 min and then determined by High-Performance Liquid Chromatography (HPLC) using acetonitrile and phosphoric acid in a 10:90 ratio as the mobile phase and octadecylsilane (C18) as the stationary phase.
 Results: The results showed a decrease in the melting point and enthalpy of fusion on the DSC thermogram, a new peak in the X-ray diffraction pattern, and a slight shift of wave number in the FTIR spectroscopy. Those characterizations indicated that the multicomponent crystal formed a salt type. SEM analysis showed morphological changes and formation of new crystal habits. The polarization microscopy analysis showed birefringent with various colors in all samples. The solubility of multicomponent crystal is 2.73-times higher compared to intact trimethoprim.
 Conclusion: The formation of cocrystals of trimethoprim and mandelic acid by SDG method increased the solubility of trimethoprim.

The Formation and Characterization of Multicomponent CrystalPiperin-Urea Using The Solvent Drop Grinding Technique

Piperine is an alkaloid found in the fruits and roots of Piper nigrum. Piperine has an almost insoluble solubility in water. Piperine has pharmacological activities such as antihypertensive andantiplatelet, antioxidant, antitumor, antiasthma, antidepressant, and hepatoprotective. This study aims to increasethesolubility of piperine by forming multicomponent crystals using urea as a coformer. Multicomponent crystals were prepared with a mole ratio of 2:1usingthe Solvent Drop Grinding method. Multicomponent crystals were characterized by X-Ray Dif raction (XRD), Dif erential Scanning Calorimetry (DSC), Fourier Transformation Infra-Red (FT-IR), Scanning Electron Microscopy (SEM), and dissolution test. The results of the multicomponent crystal characterization showed an improvement in the physicochemical properties of piperine. The x-raydiffraction pattern of the multicomponent crystals showsthe same diffractogram as the constituent components, which indicates that no new crystalline phases are formed. The DSC thermogramshows the sameendothermic peak for both components. FTIR characterizationshowed no shift in the peak of the piperine group. The SEM results did not reveal anynewcrystal habit forms. In the dissolution test, it was found that the percentage of dissolution at 60 minutes of piperine had a value of 36.148%, andamulticomponent crystal of 50.530%, this indicates that the formation of multicomponent crystals can increase the dissolution rate of piperine by 1.39 times.

Nanoparticle of Telmisartan and Polyvinylpyrrolidone K-30: Characterization and Dissolution Study

Background: Telmisartan (TEL) is an orally active nonpeptide angiotensin II antagonist drug. The drug acts on a subtype of AT1 receptors, which serves to cope with high blood pressure (hypertension). TEL is a class II Biopharmaceutical Classification System (BCS), which is a drug that has low solubility in water and high permeability. Objectives: This study aims to determine the effect of the formation of TEL-PVP K-30 nanoparticles through the solvent drop grinding method on the characteristics of physicochemical properties and the rate of dissolution of TEL. Methods: Nanoparticles are made in 2 formulas, namely formula 1: 1 and formula 1: 2. Results: Characterization of the Particle Size Analyzer (PSA) was performed with the results of the formula 1:1 24nm, and the formula 1:2 35nm. X-ray Diffraction (XRD) analysis resulted from a decrease in the intensity of crystallinity degrees. Fourier Transform Infrared (FT-IR) Spectroscopy occurs wave number shift. Differential Scanning Calorimetry (DSC) decreases in melting point. The dissolution rate was carried out using a pH 7.5 phosphate tart medium. Conclusion: The result of the dissolution rate has increased by 3.3 times for formula 1:1 and 2.9 times for formula 1:2.
 Keywords: Telmisartan; polyvinylpyrrolidone K-30; nanoparticles; and solvent drop grinding.

Solubility improvement of gallic acid in water through cocrystal formation with the solvent-drop grinding method and tartaric acid as co-former

Background: Quality, safety, and efficacy are required in pharmaceutical preparations on the market. The role of tested active substances and additives in producing a product formula that is stable, consistent, and meets standards. Solubility is an important parameter for achieving systemic drug concentration and pharmacological response. Cocrystals, for example, have been studied extensively to increase their solubility. Solvent-drop grinding is used to combine active pharmaceutical substances with co-formers into a single crystal unit. Gallic acid is an antioxidant, antimicrobial, anti-inflammatory, anticancer, cardioprotective, gastroprotective, and neuroprotective chemical compound. It is soluble in water thus used to make cocrystals. Also, tartaric acid is crystallised, inert, and easily soluble in water, so it is a natural choice as a co-former. Objectives: Solvent-drop grinding was used to characterise the gallic acid cocrystal formation with tartaric acid co-former, and the effect of gallic acid cocrystal formation with tartaric acid as a co-former was tested using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Method: The ratios of gallic acid cocrystals to tartaric acid co-formers were 1:0, 1:1, and 2:1. After crushing gallic and tartaric acids for four minutes, a few drops of ethanol solvent were added until the mixture was homogeneous. Result: There was an increase in the cocrystal solubility test. The presence of hydrogen bonds between the co-formers of gallic and tartaric acids is indicated by a wavenumber shift in the cocrystal's infrared spectrum. Furthermore, each cocrystal creates a new peak in the X-ray pattern, indicating that hydrogen bonds formed cocrystals. Conclusion: The co-crystallisation method can increase the solubility of gallic acid in water by 1.21 times.

Solubility Enhancement and Characterization of Tamoxifen Citrate Using Co-crystallization

Tamoxifen citrate (TC) is one of the anti-estrogen agents which has low solubility in the water. As TC is still used as the main therapy in breast cancer treatment, modifications are still being made to increase the solubility of TC for a successful treatment. In this research, co-crystallization of TC was performed using Nicotinamide (NIC), Isonicotinamide (ISO), Saccharin (SAC), Aspartame (ASP), and Benzoic Acid (BNZ) as a coformer with the molar ratio of 1:1, 1:2, and 2:1. Co-crystal was prepared by solvent drop grinding (SDG) and solvent evaporation (SE) methods using methanol. The results of the solubility test showed that TC-NIC and TC-ISO co-crystals with a 1:2 molar ratio made using the SDG and SE methods gave the best results. Meanwhile, the best dissolution test results were shown by TC-ISO co-crystals with a ratio of 1:2. Based on the characterization of physical stability, the SDG method resulted in more stable TC co-crystals than the SE method. Therefore, in this case, the SDG method could be more advantageous to be used for development in the field of co-crystallization.

Uracil Derivatives for Halogen-Bonded Cocrystals.

Among non-covalent interactions, halogen bonding is emerging as a new powerful tool for supramolecular self-assembly. Here, along with a green and effective method, we report three new halogen-bonded cocrystals containing uracil derivatives and 1,2,4,5-tetrafluoro-3,6-diiodobenzene as X-bond donor coformer. These multicomponent solids were prepared both by solvent-drop grinding and solution methods and further characterized by powder and single-crystal X-ray diffraction, Fourier-transformed infrared spectroscopy, and thermal methods (TGA-DSC). In order to study the relative importance of hydrogen versus halogen bonds in the crystal packing, computational methods were applied.

Preparation, characterization and evaluation of fenofibrate: benzoic acid cocrystals with enhanced pharmaceutical properties

BackgroundCocrystallization process involved the understanding of interaction at molecular level between two molecules in context to their crystal packing and designing of new solids having improved physicochemical as well as pharmaceutical properties. In the present research, an attempt to increase the aqueous solubility and dissolution rate of a poorly aqueous soluble drug fenofibrate (FB) by formulation and evaluation of its cocrystals with benzoic acid (BZ) as a coformer was carried out.ResultsThe drug and coformer were cocrystallized by using the solvent drop grinding method. For prediction of cocrystals formation, CSD (Cambridge Structure Database) software was utilized. Fourier transformation infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) techniques were used for analysis of cocrystals. Albino rats were procured from institution as per IAEC guidelines for in vivo anti-hyperlipidaemic studies. The in vitro dissolution profile of cocrystals, pure drug, their physical mixture and marketed formulation was found to be 89%, 39%, 47% and 61%, respectively.ConclusionsAn enhanced anti-hyperlipidaemic activity of cocrystals was found compared to pure drug. The FB: BZ cocrystals also compared to the pure drug showed better dissolution profile and improved in vivo anti-hyperlipidaemic activity in rats. The study proved that cocrystals can promise to improve in vitro dissolution rate of poorly aqueous soluble drugs, which in turn can lead to better in vivo activities.

Novel cocrystals of brexpiprazole with improved solubility

Brexpiprazole (BPZ) is a typical antipsychotic drug used for the treatment of schizophrenia and depression. It is classified under BCS class-II with low aqueous solubility and high intestinal permeability. In the present investigation, we reported novel solid forms of brexpiprazole with acid coformers such as glutaric acid (GLU), fumaric acid (FUM), malonic acid (MAL) and succinic acid (SUC) via solvent drop grinding method. All the cocrystals were completely characterized by PXRD (Powder X-ray Diffraction), DSC (Differential Scanning Calorimetry) and FTIR (Fourier Transform Infrared Spectroscopy). The crystal structure is determined for malonic acid cocrystal by single-crystal X-ray diffraction method. The crystal structure revealed that the cocrystal crystallized in the triclinic crystal system with space group P-1 and the malonic acid molecules are sandwiched by brexpiprazole molecules. The solubility studies for brexpiprazole and cocrystals are established in 0.05 M acetate buffer with pH 4.3 at 25 ± 2 °C. Among all solid forms BPZ:FUM cocrystal shown 2.6 times higher solubility than parent drug whereas other cocrystals such as BPZ:GLU, BPZ:SUC and BPZ:MAL improved by 1.77, 1.59 and 1.37 times.

Solid State Characterization and Dissolution Enhancement of Nevirapine Cocrystals.

Purpose: Novel cocrystals of nevirapine (NP) were designed and prepared with salicylamide and 3-hydroxy benzoic acid (3-HBA). Methods: The cocrystals were prepared by solvent drop grinding method by adding few drops of acetone to enhance the solubility and dissolution. The drug and cocrystals were characterized by differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD). The solubility of NP, its wet ground form, and cocrystals were investigated at different pH. Moreover, the effect of surfactant on solubility of cocrystals was also studied. Finally, intrinsic dissolution rate (IDR) and stability of cocrystals was examined. Results: The characterization of cocrystals by DSC and PXRD revealed formation of new solid forms due to changes in thermogram and PXRD pattern. The cocrystal of NP with 3-HBA showed 4.5 folds greater solubility in pH 1.2 buffer and 5.5 folds in 1% Tween 80 as compared to original drug. IDR of cocrystals was higher than the pure drug in 0.1 N hydrochloric acid (HCl). Moreover, cocrystals were found physically stable after 3 months as evident from unchanged IDR. Conclusion: Hence, the present research indicates the new stable solid forms of NP with improved dissolution rate than pure drug.

DISSOLUTION ENHANCEMENT OF LANSOPRAZOLE USING COCRYSTALLIZATION

Objective: Lansoprazole (LPZ) is a Biopharmaceutics Classification System Class II drug. It has low solubility and high permeability, so its rate ofdissolution is a rate-limiting step for drug absorption. This study aimed to improve the dissolution rate of LPZ by forming cocrystals, using nicotinamide(NCT) as the conformer.Methods: Cocrystals of LPZ were produced using the solvent evaporation and solvent-drop grinding methods with a molar ratio of 1:1 and 1:2.The cocrystals were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanningcalorimetry (DSC). The solubility and dissolution of the LPZ cocrystals were examined in distilled water.Results: FTIR was used to confirm the formation of hydrogen bonds between LPZ and NCT. DSC and XRD studies showed the formation of crystalsfrom cocrystals and a decrease of the melting point of the cocrystals. The dissolution study revealed that the cocrystals could increase the LPZdissolution rate by up to 8.4-fold compared with pure LPZ.Conclusion: LPZ cocrystal formation with NCT was successful in increasing the dissolution rate of LPZ.

Perbaikan Kelarutan Albendazol Melalui Pembentukan Kristal Multikomponen dengan Asam Malat

An effort to improve the solubility of albendazole (ABZ), an anthelmintic drug has been successfully carried out through the formation of multicomponent crystal with dl-malic acid (MAL). Construction of phase solubility curve of ABZ in MAL solution and crystal morphological observations after recrystallization in the acetone-ethanol (9:1) mixture were performed for initial prediction of multicomponent crystal formation. ABZ-MAL multicomponent crystal was prepared by wet grinding or also known as solvent-drop grinding (SDG) with acetone-ethanol (9:1) mixture as a solvent followed by characterization of the multicomponent crystal formation by powder X-ray diffraction and Fourier transform infrared (FTIR) methods. The solubility of ABZ-MAL multicomponent crystal was tested in water at ambient temperature and in pH 1.2, 4.5 and 6.8 of buffered solutions at 37°C. The phase solubility curve of the ABZ in the MAL solution showed type Bs. The ABZ-MAL mixture has a different crystalline morphology than pure ABZ and MAL after recrystallization in the acetone-ethanol mixture (9:1). The powder X-ray diffraction pattern and the FTIR spectrum of ABZ-MAL from SDG different from intact ABZ and MAL powder X-ray diffraction patterns and these results can indicate the ABZ-MAL multicomponent crystal formation. The ABZ-MAL multicomponent crystal has better solubility than pure ABZ in all media used. These results can be concluded that ABZ-MAL multicomponent crystal can be prepared by solvent-drop grinding method with acetone-ethanol (9:1) mixture as a solvent and can increase the solubility of albendazole.

Solubility Enhancement of Clozapine Through Co-Crystal Formation with Isonicotinamide

Clozapine (CLO) is an effective atypical antipsychotic to control the symptoms of psychosis and schizophrenia. Clozapine has low solubility and high permeability, so it is classified as a class II in the biopharmaceutical classification system. The aim of this study was to improve the solubility and dissolution rate of clozapine by clozapine-isonicotinamide (CLO-INA) co-crystal formation. CLO-INA co-crystal was prepared by solvent-drop grinding (SDG) method using water as a solvent. Characterization of SDG result was conducted by powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR). Solubility test was performed in water at room temperature. The dissolution test was performed in 900 mL of pH 6.8 phosphate buffer solution, 50 rotation per minute of paddle rotation, and at 37±0.5 °C. The PXRD pattern of SDG result of CLO-INA has many different peaks from its parent components, and this may indicate the co-crystal formation. The solubility of the co-crystal clozapine was fifteen folds higher than pure clozapine. The dissolution rate of CLO-INA co-crystal increased in the first 10 minutes compared to pure clozapine. Percentage of clozapine dissolved after 10 minutes from CLO-INA co-crystal and pure CLO were 10.2 and 2.4%, respectively. CLO and INA can form co-crystal by SDG method that can improve the solubility and dissolution rate of clozapine.Keywords: Clozapine, Isonicotinamide, Co-crystal, Solubility, Dissolution

THE DEVELOPMENT OF GLIBENCLAMIDE-SACCHARIN COCRYSTAL TABLET FORMULATIONS TO INCREASE THE DISSOLUTION RATE OF THE DRUG

Objective: Cocrystallisation is a promising method in order to increase the solubility and dissolution of poorly water-soluble drugs. The aim of this study was to prepare, formulate and evaluate glibenclamide (GCM) cocrystal in direct compress tablet dosage form using saccharin (SAC) as the coformer.
 Methods: GCM cocrystal with various stoichiometric ratios were prepared by the solvent drop grinding method. The co-crystal was characterized by a saturated solubility test and dissolution rate test, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-Ray Diffraction (PXRD). The tablet dosage form of GCM was formulated and evaluated compare with the conventional dosage form.
 Results: The solubility and disso­lution rate of GCM-SAC cocrystals increased significantly compared with pure GCM, especially for 1:2 of ratio. The dissolution rate of cocrystal with ratio 1:2 increased by almost 91.9% compared with pure GCM. Based on the FTIR analysis, it showed the shifting of characteristic bands of GCM in the spectrum and there was no chemical reaction in GCM cocrystal. In PXRD measurement, the new crystalline peak was detected in the crystal habit of cocrystal compared with pure GCM and coformer. The new single melting of GCM-SAC cocrystal also was detected in DSC measurement. The tablets of GCM-SAC cocrystal were successfully prepared by direct compression method which rapidly disintegrated (1 min) and has higher dissolution compared with its pure form (32.36% greater than glibenclamide after 45 min).
 Conclusion: The tablet dosage form of GCM cocrystal with SAC as coformer was successfully prepared, formulated and improved its solubility and dissolution rate.

The effect of surfactant and polymer on solution stability and solubility of tadalafil-methylparaben cocrystal

Cocrystal formation is a novel method to enhance physicochemical properties of pharmaceuticals. However, instability in solution is one of the challenging issues of cocrystals and surfactants/polymers could have a positive effect on cocrystal solubility and stability. In this study, tadalafil cocrystal was prepared via the solvent drop grinding method with methylparaben as a cocrystal former. The thermodynamic solubility of cocrystal was determined in phosphate buffer solution (pH = 6.8) and in the presence of different concentrations of sodium lauryl sulfate (SLS) and polyvinylpyrrolidone (PVP), followed by investigating their effects on solution stability of cocrystal. The prepared cocrystal showed enhancement in solubility compared with tadalafil, but the solution stability analysis indicated it is an incongruently saturating cocrystal that could transform to a less soluble solid form during slurring and dissolution. Moreover, PVP and SLS improved the cocrystal solution stability, however, the solubility advantage for the prepared cocrystal is not obtained because of preferential solubilization for tadalafil that is less soluble than methylparaben. Overall, the results showed that cocrystal formation of tadalafil with methylparaben has the ability to change its physicochemical properties. In addition, polymer and surfactant could have a significant effect on the solubility and the stability of the cocrystal.

KLi(HC3N3O3)·2H2O: Solvent-drop Grinding Method toward the Hydro-isocyanurate Nonlinear Optical Crystal.

A novel mixed alkali hydro-isocyanurate, KLi(HC3N3O3)·2H2O was first prepared in AOH-BOH-H3C3N3O3 (A/B = Li/Na/K/Rb/Cs) system via a solvent-drop grinding method. KLi(HC3N3O3)·2H2O shows a large second harmonic generation response (5.3 × KH2PO4) with an ultraviolet cutoff edge of 237 nm. More importantly, the bulk single crystal can be readily grown through water solution technique. Characterization of these crystals indicates that KLi(HC3N3O3)·2H2O has a high laser damage threshold (LDT) (4.76 GW/cm2) and exhibits a large birefringence (Δ n = 0.186@514 nm), which reduces Type I phase-matching to 246 nm.