DEVELOPMENT OF ORODISPERSIBLE TABLETS OF LORATADINE CONTAINING AN AMORPHOUS SOLID DISPERSION OF THE DRUG IN SOLUPLUS® USING DESIGN OF EXPERIMENTS

Objective: The objective of the present work was to develop an orodispersible tablet of loratadine, an orally active, non-sedating anti-histaminic, belonging to BCS Class II. The drug was prepared as a solid dispersion using Soluplus® as carrier and formulated into an optimal tablet using Design of Experiments.Methods: Solid dispersions of loratadine with varying ratios of Soluplus® were prepared by solvent evaporation and subjected to solubility study in simulated salivary fluid. Selected composition was characterized by differential scanning calorimetry and X-ray diffraction and formulated into an orodispersible tablet by direct compression after addition of suitable excipients. DOE based on a full factorial design was used to optimize the product using a trial version of JMP software, so as to obtain a tablet with low friability, rapid disintegration and maximal drug dissolution within 5 min. The optimized tablet was prepared and evaluated for several attributes, including in vivo disintegration and palatability.Results: A solid dispersion prepared with a 1: 4 ratio of loratadine: Soluplus® was found to show a 130-fold increase in drug solubility in the simulated salivary fluid. X-ray diffraction revealed loratadine in amorphous form. The exercise using DOE for optimization of the orodispersible tablet formula served to balance the proportion of crospovidone as super disintegrant and PVP as dry binder and yielded a formulation with good mechanical strength, rapid in vitro disintegration (39 sec) and dissolution of 93.78% of the drug within 5 min. When evaluated in vivo, the tablets were found to disintegrate in about 60 secs and were reported to be palatable.Conclusion: A patient-friendly dosage form containing a highly soluble form of loratadine was prepared and could be of potential benefit in offering quick relief from allergic conditions.

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

Preparation，physicochemical properties and pharmacokinetics in rats of CHMFL-KIT-110 solid dispersions / 中国药科大学学报

@#Solid dispersions of the insoluble compound CHMFL-KIT-110 were prepared by solvent method with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus),Poloxamer 407,PEG 6000,Copovidone (Kollidon VA64) as carriers and SLS,Tween 80,Cremophor RH40 as solubilizers. The optimal formulation was screened and obtained with dynamic solubilities and supersaturation performances as indexes. The final product was characterized by Fourier transform infrared (FT-IR),differential thermal analysis (DTA) and X-ray powder diffraction (XRPD). The stability and pharmacokinetic behavior in rats were also investigated. Results suggested that when the weight ratio of CHMFL-KIT-110/Soluplus/SLS was 1∶4∶0.5,dynamic solubility of the solid dispersions was significantly improved with no recrystallization. In the accelerated condition (40 °C,75% RH) for 30 days,CHMFL-KIT-110 in the solid dispersions was still amorphous with no crystal observed. The results of pharmacokinetics in rats showed that the cmax and AUC0→t of CHMFL-KIT-110 solid dispersions were 373.1 times and 358.7 times higher than those of free drugs,respectively. These results help to understand the formulation development and clinical practice of CHMFL-KIT-110.

Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.