Spray-Dried Amorphous Solid Dispersions of Simvastatin,a Low T<Subscript>g</Subscript> Drug: <Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">in Vivo</Emphasis> Evaluations

Purpose To obtain free flowing, stable, amorphous solid dispersions (SDs) of simvastatin (SIM), a drug with relatively lower glass transition temperature (T_g) by spray drying technique, and to perform comparative in vivo study in rats, which could justify the improvement in rate and extent of in vitro drug release.Methods Dichloromethane suspensions of SIM either alone or in combination with PVP (1:1 or 1:2 parts by weight) were spray dried with proposed quantity of Aerosil 200 (1:1, 1:1:1, 1:2:2 parts by weight of SIM, Aerosil 200 and PVP, respectively). SDs were characterized initially in comparison with pure drug and corresponding physical mixtures in same ratios by drug content, saturation solubility, SEM, DSC, XRPD, IR, and in vitro drug release. SD 1:2:2 was further subjected to accelerated stability testing and checked for in vitro drug release and presence of crystallinity using DSC and XRPD. In addition, improvement in rate and extent of in vitro drug release from SD 1:2:2 was justified by in vivo study in rats.Results Combination of SD and surface adsorption techniques has been attempted to overcome the limitations of spray drying technique for amorphization of low T_g drugs. Based on powder characteristics, drug content, saturation solubility, and feasibility of processing into tablets; SD 1:2:2 was selected as the optimized formulation. During initial characterization, SEM, DSC, and XRPD analyses confirmed the presence of amorphous form in SD 1:2:2. IR spectroscopy revealed possibility of hydrogen bonding interaction between SIM and PVP in SDs. Also, there was dramatical improvement in rate and extent of in vitro drug release of SD 1:2:2. Insignificant decrease in dissolution was observed with no evidence of crystallinity during accelerated stability studies of SD 1:2:2. Moreover in vivo study in rats also justified the improvement in therapeutic efficacy of SD 1:2:2 over pure SIM.Conclusions Thus, present study demonstrates high potential of spray drying technique for obtaining stable amorphous SDs of low T_g drugs.     

The Synergetic Effects of Nonpolar and Polar Protic Solvents on the Properties of Felodipine and Soluplus in Solutions,Casting Films,and Spray-Dried Solid Dispersions

The aim was to explore the effects of nonpolar and polar protic solvents composed of dichloromethane (DCM) and ethanol (EtOH) on the properties of felodipine (FLDP) and Soluplus in solutions, casting films, and spray-dried drug-rich or polymer-rich solid dispersions (SDs). Measurement of intrinsic viscosity and solubility indicated that FLDP and Soluplus were miscible. EtOH-DCM ranging from 20:80 to 50:50 induced the strongest molecular interactions for FLDP-Soluplus-solvents systems. Accordingly, the casting films and spray-dried powders of FLDP and Soluplus were prepared using pure EtOH or DCM and their mixtures as solvents. Polarized light microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, in vitro dissolution tests, and stability have been conducted to characterize these films or spray-dried powders. EtOH-DCM (50:50) showed δ_H 2-3 MPa^1/2 higher than FLDP and Soluplus. It exhibited stronger inhibitory effects on phase separation and recrystallization of amorphous FLDP than pure DCM or EtOH in the drug-rich casting films, spray drying process, and spray-dried SDs exposure to 40°C/RH75% for 1 month. Higher ratio of Soluplus may offset the effects of solvents on the dissolution and stability of polymer-rich SDs. In conclusion, combination of nonpolar and polar protic solvents is of high potential for spray drying to optimize drug-rich SDs.     

Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates

Introduction: Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs.

Areas covered: The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize^?, closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug–carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, Solumer^TM used to prepare stable amorphous SD.

Expert opinion: Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.     

Preparation and characterisation of lornoxicam solid dispersion systems using hot melt extrusion technique

The aim of the research study was to investigate the ability of Soluplus^® and surfactant individually as well as in combination to improve the solubility, subsequently the dissolution profile of lornoxicam (LORX). A laboratory size single screw rotating extruder with temperature and speed control parameters employed during hot melt extrusion (HME) processing of LORX along with polymer-surfactant blends. Soluplus^® used as primary solubilizing agent for preparing solid dispersion (SD). Along with Soluplus^® different concentrations of surfactants such as PEG 400, Lutrol F127, Lutrol F68 were used to solve the permeability issues related to LORX. Encapsulation of LORX particles inside the molten matrix of polymer-excipient blend was confirmed by DSC, XRD and FT-IR. Drug excipient microscopic interaction was further confirmed by scanning electron microscopy (SEM). Depending upon the ratio of the polymer and surfactants used, the solubility of the hot melt extruded LORX was improved and found to be in the range 35–86 μg/ml (actual aqueous solubility of LORX was found to be 0.0083 μg/ml). Dissolution profile of the extruded SD was improved and was found to be in the range of 98–104 % within 20 min (actual dissolution profile of LORX was found to be 8 % at the end of 1 h). SEM and Raman images suggest the formation of amorphous dispersion systems. SD was subjected to stability studies as per ICH guidelines and found to be stable after 6 months when analyzed by HPLC. SD prepared from HME significantly improves the solubility and dissolution profile of LORX—a BCS class II drug.     

Formulation of highly purified fenugreek gum based silica lipid drug delivery system for simvastatin with enhanced dissolution rate and in vitro characterization

In current study, highly purified fenugreek gum (HPFG) isolated by patented method explored as emulsifier and hydrophilic solid carrier in drug delivery system. Anti-hyperlipidemic drug simvastatin (SIM) was selected as drug model for the study as it is associated with poorly water solubility and low bioavailability problems (<5 %). A suitable HPFG-based silica lipid system composed of SIM (1.5 %), medium chain triglyceride Capmul^® MCM (10 %) as lipid phase, 0.6 % HPFG as emulsifier and HPFG 2.5 %, different grades colloidal silica (7.5 %) (Aerosil^® 300 Pharma, Aerosil^® 380 Pharma and Aeroperl^® 300 Pharma) as hydrophilic solid carriers was developed. The optimized HPFG-based silica lipid systems were characterized for physical characteristics like flow ability, compressibility, redispersiblity, solubility and in vitro drug release using USP apparatus II in pH 6.8 phosphate buffer. The system was also characterized for Fourier transform infrared spectroscopy, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The developed formulation was found to have excellent flow property, readily redispersiblity, better aqueous solubility and showed 3–4-fold increase in dissolution rate as compared to plain drug and marketed formulation (Simlo^® 10). Transition of crystalline drug to amorphous state was confirmed by DSC, PXRD and SEM studies. Enhanced dissolution rate and solubility possibly attributed to improved wetting, amorphous drug state and facilitated diffusion from lipid-based system. Thus developed HPFG-based silica lipid system provides an alternative means for SIM with enhanced dissolution rate and stability in oral solid dosage form.     

Increased dissolution and oral absorption of itraconazole/Soluplus extrudate compared with itraconazole nanosuspension

The purpose of this article was to compare the in vitro and in vivo profiles of itraconazole (ITZ) extrudates and nanosuspension separately prepared by two different methods. And it was proved truly to form nanocrystalline and amorphous ITZ characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform infrared spectrum (FTIR), transmission electron microscope (TEM), and scanning electron microscope (SEM). The release of ITZ/Soluplus solid dispersions with amorphous ITZ was almost complete while only 40% release was obtained with ITZ nanocrystals. The amorphous state need not to cross over the crystal lattice energy upon dissolution while the crystalline need to overcome it. In the in vivo assay, the AUC(0–t) and C_max of ITZ/Soluplus were 6.9- and 11.6-time higher than those of pure ITZ. The formulation of the extrudate had an AUC(0–t) and C_max similar to those of ITZ and also OH-ITZ compared with the commercial capsule (Sporanox®). The relative bioavailability values with their 95% confidence limit were calculated to be 98.3% (92.5–104.1%) and 101.3% (97.9–104.1%), respectively. The results of this study showed increased dissolution and bioavailability of the solid dispersion of Soluplus-based carrier loading ITZ prepared by HME compared with the ITZ nanosuspension prepared by wet milling.     

Overcoming formulation challenges for the next generation of vaccines

Introduction: In recent years, the number of active pharmaceutical ingredients with high therapeutic impact, but very low water solubility, has increased significantly. Thus, a great challenge for pharmaceutical technology is to create new formulations and efficient drug-delivery systems to overcome these dissolution problems.

Areas covered: Drug formulation in solid dispersions (SDs) is one of the most commonly used techniques for the dissolution rate enhancement of poorly water-soluble drugs. Generally, SDs can be defined as a dispersion of active ingredients in molecular, amorphous and/or microcrystalline forms into an inert carrier. This review covers literature which states that the dissolution enhancement of SDs is based on the fact that drugs in the nanoscale range, or in amorphous phase, dissolve faster and to a greater extent than micronized drug particles. This is in accordance to the Noyes–Whitney equation, while the wetting properties of the used polymer may also play an important role.

Expert opinion: The main factors why SD-based pharmaceutical products on the market are steadily increasing over the last few years are: the recent progress in various methods used for the preparation of SDs, the effect of evolved interactions in physical state of the drug and formulation stability during storage, the characterization of the physical state of the drug and the mechanism of dissolution rate enhancement.     

Effect of Soluplus on the supersaturation and absorption of tacrolimus formulated as inclusion complex with dimethyl-β-cyclodextrin

The application of tacrolimus (FK506) is hampered by its poor solubility and dissolution, which can be promoted by the use of inclusion complex. However, in supersaturated environment, crystallization of the drug inclusion complex may occur, leading to reduced absorption in vivo. In this study, Soluplus, an amphiphilic copolymer of polyvinyl caprolactam, polyvinyl acetate and polyethylene glycol, was used to improve the supersaturated stability and absorption of FK506. Using dimethyl-β-cyclodextrin (DM-β-CD), the inclusion complex (FK506-CD) was prepared, which showed favorable dissolution profiles. But in supersaturated condition, the drug concentration was rapidly decreased, with 10.64?±?0.69?μg/ml of FK506 at 12?h. Ternary complex (FK506-SCD) containing Soluplus contributed steadier drug concentration. The FK506-SCD with 1.2% Soluplus best promoted the supersaturated stability of the inclusion complex, with 62.90?±?3.34?μg/ml of FK506 at 12?h. Soluplus also reduced the crystallization and degradation of FK506 in the stress test. In the single-pass intestinal perfusion test, the absorption of FK506 in the ileum and colon was significantly increased. Pharmacokinetic results showed that the bioavailability of FK506-SCD was 2.34-fold that of FK506-CD. Our data suggested that Soluplus had an excellent capability in improving the supersaturated stability and in vivo absorption of FK506 inclusion complex.     

Characterization of Solid Dispersion of Itraconazole Prepared by Solubilization in Concentrated Aqueous Solutions of Weak Organic Acids and Drying

Purpose

The purpose of this study was to develop an amorphous solid dispersion (SD) of an extremely water-insoluble and very weakly basic drug, itraconazole (ITZ), by interaction with weak organic acids and then drying that would enhance dissolution rate of drug and physical stability of formulation.

Methods

Aqueous solubility of ITZ in concentrated solutions of weak organic acids, such as glutaric, tartaric, malic and citric acid, was determined. Solutions with high drug solubility were dried using vacuum oven and the resulting SDs having 2 to 20% drug load were characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. The dissolution of SDs was initially studied in 250 mL of 0.1 N HCl (pH 1.1), and any undissolved solids were collected and analyzed by PXRD. The pH of the dissolution medium was then changed from 1.1 to 5.5, particle size of precipitates were measured, and drug concentrations in solution were determined by filtration through membrane filters of varying pore sizes.

Results

The aqueous solubility of ITZ was greatly enhanced in presence of weak acids. While the solubility of ITZ in water was ~4 ng/ mL, it increased to 25–40 mg per g of solution at 25°C and 200 mg per g of solution at 65°C at a high acid concentration leading to extremely high solubilization. PXRD of SDs indicated that ITZ was present in the amorphous form, wherein the acid formed a partially crystalline matrix. ATR-FTIR results showed possible weak interactions, such as hydrogen bonding, between drug and acid but there was no salt formation. SDs formed highly supersaturated solutions at pH 1.1 and had superior dissolution rate as compared to amorphous drug and physical mixtures of drug and acids. Following the change in pH from 1.1 to 5.5, ITZ precipitated as mostly nanoparticles, providing high surface area for relatively rapid redissolution.

Conclusions

A method of highly solubilizing an extremely water-insoluble drug, ITZ, in aqueous media and converting it into an amorphous form in a physically stable SD was successfully investigated. The dissolution rate and the extent of supersaturation of the drug in dissolution media improved greatly, and any precipitate formed at high pH had very small particle size.

     

Bicalutamide nanocrystals with improved oral bioavailability: in vitro and in vivo evaluation

Context: Bicalutamide (BCT) is an antiandrogenic compound belonging to Biopharmaceutics Classification System (BCS) class II drug. Thus it has limited aqueous solubility and hence limited oral bioavailability.

Objective: The purpose of the present investigation was to obtain stable nanocrystals of BCT with improved kinetic solubility, dissolution and pharmacokinetic profiling.

Materials and methods: BCT nanocrystals were prepared by antisolvent precipitation method using Soluplus, a novel amphiphilic polymer. Nanocrystals were characterized for particle size, powder X-ray diffraction analysis (PXRD), in vitro dissolution, in vivo pharmacokinetic profile and stability.

Results and discussion: The obtained nanocrystals had particle size of 168 nm and were spherical in shape. The nanocrystals exhibited fivefold increase in kinetic solubility as compared to pure drug and 85% dissolution in 60 min. PXRD studies established the retention of crystalline polymorphic form II. The in vivo pharmacokinetic study demonstrated that the C_max and AUC of nanosized BCT were about 3.5 times higher as compared to pure drug.

Conclusion: Nanosizing of BCT significantly improved the pharmacokinetic profile of the drug administered to rats. Prepared nanocrystals were found to be stable over the entire stability period. Thus the use of amphiphilic polymer like Soluplus singularly helped in efficient size reduction and stabilization of the drug.     

Dissolution enhancement of felodipine by amorphous nanodispersions using an amphiphilic polymer: insight into the role of drug–polymer interactions on drug dissolution

Context: Felodipine, a poorly soluble drug, is widely used in the treatment of angina pectoris and hypertension.

Objective: This study aimed at the preparation of amorphous solid dispersion (SD) of felodipine using an amphiphilic polymer, soluplus, for the potential enhancement in solubility of the drug.

Materials and methods: Solid dispersions with varying proportions of drug and soluplus were prepared and the rate and extent of dissolution from SDs was compared with that of the pure drug. FT-IR and ¹H NMR spectroscopic analysis were carried out to examine the formation mechanism of SDs. Various techniques were used for solid state characterization of designed SDs.

Results: Formation of amorphous solid dispersions with particle size in nanometer range indicated suitability of polymer and method used in the preparation. FT-IR and ¹H NMR spectroscopy revealed that soluplus was involved in strong hydrogen bonding with felodipine molecules which resulted in the conversion of crystalline felodipine into amorphous form. Solid dispersion with 1:10 drug/polymer ratio showed more than 90% drug dissolution in 30?min whereas pure felodipine showed less than 19% drug dissolution in 1?h.

Discussion and conclusion: Amorphous SDs of felodipine were prepared using soluplus resulting in substantial enhancement in the rate and extent of dissolution of felodipine.     

Application of hot-melt extrusion technology for designing an elementary osmotic pump system combined with solid dispersion for a novel poorly water-soluble antidepressant

TP1 is a novel antidepressant with poor solubility. To reduce fluctuations in blood concentration and increase oral bioavailability, a controlled-release system was developed by combining a solid dispersion (SD) and an elementary osmotic pump (EOP). The study compared different methods of preparing SDs. Hot-melt extrusion (HME) exhibited clear advantages over the traditional melting technique. An in vitro release study demonstrated that HME-EOP tablets released TP1 in a zero-order manner over 12?h and the drug release was in dependent of the release medium and agitation speed, whereas release from molten-EOP tablets lasted only 8?h. In contrast to immediate-release tablets, the HME-EOP tablets exhibited less fluctuation in blood concentration and higher bioavailability in vivo. In summary, the osmotic pump system combined with an HME-based SD of TP1 presented controlled release in vitro, high bioavailability in vivo and a good in vivo–in vitro correlation.     

Surface-active derivative of inulin (Inutec® SP1) is a superior carrier for solid dispersions with a high drug load

The aim of this study was to compare the applicability of inulin, its surface-active derivative (Inutec? SP1), and polyvinylpyrrolidone (PVP) as carriers in high drug load solid dispersions (SDs) for improving the dissolution rate of a range of lipophilic drugs (diazepam, fenofibrate, ritonavir, and efavirenz). The SDs were prepared by spray freeze-drying. Scanning electron microscopy showed that the obtained samples were highly porous spherical particles. Modulated differential scanning calorimetry showed that the drugs incorporated in these carriers were fully or partially amorphous. The solubility of the drugs in solutions of the different carriers was increased in an order: inulin 2.3 kDa < PVP K30 ? Inutec? SP1. The dissolution behavior of SD tablets was evaluated. Inutec? SP1-based SD tablets showed the best performance followed by PVP- and inulin-based SD tablets. The superior dissolution behavior of the drugs from Inutec? SP1-based SDs could be ascribed to its surface-active nature. In addition, Inutec? SP1-based SD tablets gave good physical stability at 20 °C/45% relative humidity (RH) and 40 °C/75% RH for 3 months.     

Enhanced solubility and dissolution of simvastatin by HPMC-based solid dispersions prepared by hot melt extrusion and spray-drying method

The objective of this study was to use low viscosity grade hydroxypropyl methyl cellulose (Methocel^® E3 LV and Methocel^® E5 LV) to enhance the solubility and dissolution of poorly water soluble drug simvastatin (SIM). Two different technologies, hot melt extrusion and spray drying were employed. Characterization of hot melt extrudes and spray dried samples was done by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies and scanning electron microscopy. The result of the study showed the conversion of crystalline form drug into amorphous form indicating increase in dissolution rate and solubility of SIM.     

Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation

The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol HS15 and HPMC 2910. Solubility of biochanin A was enhanced by 8-60 folds as the drug-carrier ratio was increased in SDs. Furthermore, compared to pure biochanin A or physical mixture (PM), SDs significantly improved the dissolution rate and the extent of drug release. Particularly, SDs (Drug:Solutol HS15:HPMC 2910=1:5:5 or 1:10:10) achieved the rapid and complete drug release (approximately 100% within 1h) at pH 6.8. The XRD patterns indicated that SDs might enhance the solubility of biochanin A by changing the drug crystallinity to amorphous state in addition to the solubilizing effect of hydrophilic carriers. The improved dissolution of biochanin A via SD formulation appeared to be well correlated with the enhanced oral exposure of biochanin A in rats. After an oral administration of SD (Drug:Solutol HS15:HPMC 2910=1:10:10), C(max) and AUC of biochanin A were increased by approximately 13 and 5 folds, respectively, implying that SDs could be effective to improve the bioavailability of biochanin A. In conclusion, solid dispersion with Solutol HS15 and HPMC 2910 appeared to be promising to improve the dissolution and oral exposure of biochanin A.     

Effect of poloxamer on physicochemical properties of tacrolimus solid dispersion improving water solubility and dissolution rate

Tacrolimus (TCR; also FK-506 and trade name prograf^?), an antibiotic of macrolide family and a novel immunosuppressive agent, is a natural product of actinomycete Streptomyces tskubaensis. But TCR is poorly soluble in water (0.012?mg/mL), so its bioavailability is low and irregular. The aim of this study is to characterize physicochemical properties of TCR and investigate the improvement of solubility and dissolution rate of TCR solid dispersion (SD) with poloxamer. TCR SDs, consisting of various grades and ratios of poloxamer were prepared by hot-melting method and were characterized by DSC, PXRD, and FT-IR. The dissolution profile and solubility of TCR from the SDs were evaluated. SD of TCR prepared with poloxamer 188 at the ratio of 1:1 by the hot-melting method resulted in a significant increase in TCR solubility and enhanced dissolution profile over the TCR crystalline powder.     

Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with Gelucire 50/13

The objective of the study was enhancement of dissolution of poorly soluble carvedilol by solid dispersions (SDs) with Gelucire 50/13 using solvent evaporation method. The solubility of carvedilol showed linear increase with increasing concentrations of Gelucire indicating A_L type solubility diagrams. SDs characterized for physicochemical characteristics using differential scanning calorimetry and X-ray diffractometry revealed transformation of crystalline form of drug to amorphous form which was confirmed by scanning electron micrographs. Further fourier transform infrared spectroscopy results suggested there is no drug carrier interaction. From the dissolution parameters such as mean dissolution time, dissolution efficiency and drug release rate, improved dissolution characteristics for SDs were observed compared with physical mixture and pure drug. Thus SDs of carvedilol in Gelucire 50/13 showed enhanced solubility and dissolution rate compared to pure drug.     

Improved pH-independent dissolution and oral absorption of valsartan via the preparation of solid dispersion

This study aimed to improve the pH-independent solubility and dissolution characteristics of valsartan via the preparation of solid dispersions (SD) with poloxamer 407. SDs was prepared by using the solvent method at various drug-polymer ratios and their dissolution characteristics were examined at different pHs. Oral pharmacokinetics of SDs was also evaluated in rats. Compared to the untreated powder, SDs significantly improved the dissolution rate as well as the extent of drug release at low pH. Particularly, SD having the drug-polymer ratio of 1:5 exhibited pH-independent dissolution of valsartan, resulting in the rapid and complete drug release over the pH range of 1.2 to 6.8. The improved dissolution of valsartan via SD formulation appeared to be well correlated with the enhanced oral exposure of valsartan in rats. SDs increased C_max and AUC_0–24 of valsartan by 2–7 folds in rats, implying that SDs should be effective to improve the bioavailability of valsartan. In conclusion, SDs containing poloxamer 407 appeared to be effective to improve the pH-independent dissolution and oral absorption of valsartan.     

Molecular Mechanisms Involved in Supersaturation of Emodin Ternary Solid Dispersions Based on Bonding Agents

The use of solid dispersions (SDs) is an established method for improving the dissolution rate of poorly water-soluble drugs. However, there have been few studies on the molecular mechanisms contributing to SD supersaturation. Emodin ternary SDs (TSDs) were prepared by hot melt extrusion (HME) using Kollidon® VA64 as the polymer carrier and nicotinamide as the bonding agent. Molecular docking and solubility tests were used to assist screening of polymer carriers, and in vitro dissolution and dissociation constant data were used to optimize the formulation. A variety of analytical methods and molecular dynamics simulations were used to investigate the mechanism of SD supersaturation at the molecular level. The results showed that molecular migration, intermolecular interactions, drug crystal transformation and dissociation constant were particularly important factors in SD supersaturation. This study proposes a new strategy to improve solubility of poorly water-soluble drugs and explore the molecular mechanisms of TSD supersaturation, which could provide a basis for the rational selection of excipients for pharmaceutical preparations.     

Enhancement of Solubility and Dissolution Rate of Loratadine with Gelucire 50/13

The objective of the current investigation was to enhance the solubility and dissolution rate of loratadine using solid dispersions (SDs) with Gelucire 50/13. SDs of loratadine using Gelucire 50/13 as carrier were prepared by the solvent evaporation method, characterized for drug content, dissolution behavior, and physicochemical characteristics by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) studies. At 10 % concentration of Gelucire 50/13, the increase in solubility was around 100-fold compared with pure drug. The solubility of loratadine in the presence of Gelucire 50/13 in water showed linear increase with increasing concentrations of Gelucire indicating A_L-type solubility diagrams. The mean dissolution time (MDT) of loratadine decreased after preparation of SDs with Gelucire 50/13 indicating increased dissolution rate. FTIR studies showed the stability of loratadine and the absence of a well-defined interaction. DSC and XRD studies revealed the amorphous state of loratadine in SDs which was further confirmed from SEM. From the dissolution parameters, it is evident that the solubility and dissolution rate of loratadine was enhanced by SDs with Gelucire 50/13.