KARAKTERISASI FISIKOKIMIA NANOKRISTAL EKSTRAK HERBA SELEDRI ( Apium graveolens L.) DENGAN PERBEDAAN KONSENTRASI POLOXAMER188

Celery (Apium graveolens L) is a plant of Apiaceae family which contains flavonoids, saponins, tannins, essential oils, apiin, apigenin, choline, asparagine, vitamin A, B, C. Apigenin contained in celery included in the BCS (Biopharmaceutics Classification System) class II, which has low solubility and high permeability drugs. One method for increasing solubility is the nanocrystal method. Where the purpose of this study was to see the effect of differences in the concentration of poloxamer 188 on the characterization of nanocrystal. The results of the particle size analyzer (PSA) showed particle size distribution in formula 1 the concentration of poloxamer 188 40% 6 hour grinding time of 1648.5 nm with a potential zeta value of -11.2. While the formula 2 concentration of poloxamer 188 50% and formula 3 the concentration of poloxamer 188 60% with a 5 hour grinding time of 1049.6 and 1483.2 with a potential zeta value of -12.5 and -8.9. From the FT-IR analysis shows the presence of clusters in formulas 1, 2, and 3 which are not found in apigenin which is a celery marker compound, on the contrary there are groups on apigenin which are not found in formulas 1, 2, and 3.

Insight into Delivery Approaches for Biopharmaceutics Classification System Class II and IV Drugs

: Formulation development of BCS Class II and IV drugs is a challenging task due to their poor solubility and permeability issue. : An extensive literature survey was conducted to explore the relevant pharmaceutical approaches that have been used for solving the issue of poor solubility and permeability in the recent past. : It has been found that a plethora of approaches have been investigated for addressing the issue of poor solubility and or permeability. These include physical modifications (modification of crystal habit, particle size reduction, complexation, polymorphism and drug dispersion in carriers), chemical modifications (salt formation), and formulation modifications (Nanotechnology-based approaches and hydrotropy). : The physical and chemical modification approaches can be effectively used to enhance the solubility and dissolution rate of poorly soluble drugs, but the additional problem of poor permeability has been better addressed by lipid-based drug delivery systems. As the latter presents the drug in the solubilized state, bypass first-pass effects, circumvent the effect of Para-glycoprotein mediated efflux of drugs, hence contributing to overall bioavailability enhancement.

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.

Tuning solubility and stability of hydrochlorothiazide co-crystals

Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotinamide, succinamide,p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N—H...O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal withp-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5–2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.