Drug Dissolution Rate Research Articles

Impregnation of Fenofibrate on mesoporous silica using supercritical carbon dioxide

Low oral bioavailability can be circumvented by the formulation of the poorly water soluble drug in ordered mesoporous silica (OMS-L-7). Fenofibrate is an orally administered, poorly water-soluble active pharmaceutical ingredient (API), used clinically to lower lipid levels. Fenofibrate was loaded into silica using two methods: incipient wetness and supercritical impregnation. This study investigates the impact of loading and the impact of varying supercritical carbon dioxide (scCO2) processing conditions. The objective is to enhance Fenofibrate loading into silica while reducing degree of the drug crystallinity, so as to increase the drug's dissolution rate and its bioavailability. The comparison of both impregnation processes was made in terms of impregnation yields and duration as well as physical characterization of the drug.While incipient wetness method led to a Fenofibrate loading up to 300mgdrug/gsilica in 48h of impregnation, the supercritical impregnation method yielded loading up to 485mgdrug/gsilica in 120min of impregnation duration, at 16MPa and 308K, with a low degree of crystallinity (about 1%) comparable to the crystallinity observed via the solvent method. In addition to the enhancement of impregnation efficiency, the supercritical route provides a solvent-free alternative for impregnation.

Impact of process parameters on Mg–St content and tablet surface wettability in the external lubrication method for a rotary tablet press

External lubrication is a new alternative used in compression processes of the pharmaceutical industry to minimize the negative effect of lubricant and to resolve sticking problems. This method can also prevent the deterioration of tablet properties; e.g., reduced tensile strength and a retarded rate of drug dissolution. The current study prepared tablets using the external lubrication method with varying potential critical process parameters and clarified the process of external lubrication via statistical analysis. In accordance with past results, tablets prepared using the external lubrication method had better tablet properties (higher hardness and more rapid disintegration) than those prepared using the internal lubrication method. Quantitative analyses of the magnesium stearate content and contact angle showed that the wettability of the tablet surface increased with the magnesium stearate content. Analysis of variance showed that all potential critical parameters are influential for the magnesium stearate content, but not for the disintegration of tablets. In addition, predictions of the magnesium stearate content and disintegration time of tablets made using a model equation correlated well with observed values. The external lubrication method can thus be applied by identifying the critical process parameters in the compression process during the development and manufacture of pharmaceutical products.

Innovative oral spray-dried Idebenone systems to improve patient compliance

Idebenone is a high permeable drug with very slight water solubility that affects the dissolution rate in the biological fluids, causing an irregular and limited in vivo absorption after oral administration. Moreover, it is marketed in Europe as tablets equivalent to 150 mg, with the consequent administration of multiple dose of solid unit to obtain the correct dose, a deterrent for the patients’ compliance. According to these considerations, our goal was to develop spray-dried microparticles using a soluble β-cyclodextrin (CD) polymer and an enhancer of dissolution rate, such as carboxymethyl cellulose, to obtain a formulation easily dosable and soluble in water. The complex in solution was evaluated by phase solubility studies and the Idebenone/CD molar ratio selected was 1:1. According to Higuchi and Connors, adding carboxymethyl cellulose, a Bs-type profile was obtained. This result was due to the presence of carboxymethyl cellulose that competes with the CD in forming Idebenone microsystems, reducing of 10-fold the formulation bulk. UV–Vis absorption, 1H nuclear magnetic resonance and circular dichroism showed the formation of the CD/Idebenone inclusion complex confirmed also by differential scanning calorimetry, Fourier transform infrared spectroscopy and fluorescence microscope (FM). The water solubility data and the in vitro dissolution tests performed in simulated gastric fluid, showed an increase of the drug water interaction due to the presence of the CD and carboxymethyl cellulose, both able to improve drug wettability, water solubility and dissolution rate. This approach seems to be suitable to produce microsystems which are able to enhance the in vivo absorption of Idebenone after oral administration and to increase the patient compliance.

Preparation of a novel starch-derived three-dimensional ordered macroporous carbon for improving the dissolution rate and oral bioavailability of water-insoluble drugs

In our study, soluble starch was applied as a novel carbon source for preparing three-dimensional ordered macroporous carbon (3DOMC) using monodisperse silica nanospheres as the hard template. The 3DOMC was used as an insoluble drug carrier when it was found that it could markedly improve the water solubility of felodipine (FDP). The structural features of 3DOMC were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The 3DOMC structure was found to have a higher drug loading than microporous and mesoporous structures, and the interconnected nanostructure effectively inhibited the formation of drug crystals. FDP, belonging to the Biopharmaceutics Classification System II (BCSII), was chosen as the model drug and was loaded into the 3DOMC structure by solvent evaporation. The state of FDP in the 3DOMC structure was characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The results obtained showed that FDP was present in the pores in an amorphous or microcrystalline state. In vivo and in vitro experiments indicated that 3DOMC could significantly improve the drug dissolution rate, but the FDP-3DOMC self-made common tablets had the disadvantage of a burst effect. For this reason, osmotic pump technology was used to control the drug release rate. We developed a potentially useful insoluble drug carrier for pharmaceutical applications.

In situ niosome forming maltodextrin proniosomes of candesartan cilexetil: In vitro and in vivo evaluations

The aim of this study is to develop novel proniosomal tablets of candesartan cilexetil. Drug loaded proniosomes were prepared as dry powder by slurry method. The critical parameters of the production process were the type of the carrier (sorbitol, maltodextrin, and lactose), addition of charge inducers, rotation speed of the rotavapor and solvent evaporation temperature. The effects of these parameters on proniosome specifications such as the recovery, drug loading, drug release were investigated and also the influence on the particle size and surface charge of the niosomes derived by the hydration of proniosomes were evaluated. The mean particle size and drug loading of niosomes formed from the hydrated proniosomes were 204±2nm and 99.09±0.04% respectively, with a negative charge −43.65±0.54mV. The proniosomes demonstrated good flowability, compressibility and consolidation properties both alone and together with the tableting agents (microcrystalline cellulose and cross-linked poly vinylpyrrolidone). The niosomes derived by the hydration of proniosomal tablets preserved their initial properties. Compatibly with the increased in vitro drug dissolution rate, the relative bioavailability of drug from proniosomal tablets increased 1.86-fold and 2.75-fold and higher candesartan plasma levels were achieved within shorter time compared to the pure drug.

The Effect of Tween 20, 60, and 80 on Dissolution Behavior of Sprionolactone in Solid Dispersions Prepared by PEG 6000.

Solid dispersions have been efficient in improving the dissolution rate and bioavailability of hydrophobic drugs. The aim of the present study was enhancement of the dissolution profile of Spironolactone using solid dispersion. Spironolactone solid dispersions (1:1, 1:2 and 2:1 drug: carrier weight ratio) were prepared by polyethylene glycol (PEG) 6000 as a carrier by hot melt method. The influence of several amounts of Tween 20, 60, and 80 were also studied. The dissolution profile was evaluated by USP Apparatus II. The results showed that solid dispersions were efficacious to enhance the dissolution rate of Spironolactone in water; and the procedure indicated that there was an increase in dissolution rate for solid dispersions containing the surfactant Tweens. The solid dispersions were evaluated using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and Differential Scanning Calorimetry (DSC) studies; and the results showed no complex formation or change in crystal shape of drug. It is concluded that solid dispersion technique can be successfully used for improvement of dissolution of Spironolactone.

Design of a novel type IV lipid-based delivery system for improved delivery of drugs with low partition coefficient

Context: The physicochemical properties of drugs such as partition coefficient play a major role in the development of lipid-based drug delivery systems. The major obstacle lies in encapsulation of a drug with low partition coefficient into these systems.Objective: The objective of this study was to design and optimize a novel lipid-based delivery system with higher loading, improved pharmacokinetics consequently enhancing the oral bioavailability of drugs with low partition coefficient like valsartan.Materials and methods: The optimized formulation consists of Capryol 90, Cremophor RH 40, and Transcutol HP. Pseudo ternary phase diagrams were used to optimize the components and their concentrations in the formulation. Dissolution studies of the selected formulations were compared with plain drug and marketed product at three pH conditions (pH 1.2, 4.5 and 6.8). Pharmacokinetic parameters of optimized formulations were determined in Wistar rats and compared with that of plain drug.Results and discussion: The optimized formulation with a mean particle size of 50 nm showed significant improvement (p < 0.05) in dissolution rate with pH independence compared to plain drug and marketed product. The in vivo studies in Wistar rats revealed about 2.30- and 1.68-fold increase in the oral bioavailability and Cmax of valsartan from lipid-based formulation compared to plain drug.Conclusion: The engineered formulation strategy by type IV lipid-based formulations can be successfully exploited to improve the dissolution rate and oral deliverability of drugs like valsartan.

Development of a novel starch with a three-dimensional ordered macroporous structure for improving the dissolution rate of felodipine.

In this study, silica nanospheres with different particle sizes were used as hard template for synthesis of a starch with a novel three-dimensional ordered macroporous structure (3DOMTS). As a pharmaceutical adjuvant, 3DOMTS was used to improve the dissolution rate and oral relative bioavailability of water-insoluble drugs. Felodipine (FDP) was chosen as a model drug and was loaded into the 3DOMTS by solvent evaporation. FDP loading into 3DOMTS with different pore sizes was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimeter (DSC), powder X-ray diffractometer (PXRD) and Fourier-Transform Infrared (FTIR). The results obtained showed that FDP was present in the pores in an amorphic or microcrystalline state. The in vitro dissolution results showed that 3DOMTS could effectively improve the dissolution rate of FDP in comparison with commercial common tablets. Pharmacokinetic results indicated that the oral relative bioavailability of self-made FDP-3DOMTS tablets were 184%, showing that 3DOMTS produced a significantly increased oral absorption of FDP. In conclusion, 3DOMTS exhibits the dual potential of improving the dissolution rate of poorly water soluble drugs and the novel filler produced by direct compression technology confirming that 3DOMTS will be useful for many applications in the field of pharmaceutics.

Pharmacological and histological examination of atorvastatin-PVP K30 solid dispersions

The objective of the present study was to investigate the pharmacological efficiency of orally administered atorvastatin calcium (ATV) solid dispersions (SDs). SDs of ATV were prepared using polyvinylpyrrolidone K30 (PVP) through the solvent evaporation method. Physicochemical characteristics of the prepared formulations were assessed benefitting scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). The drug dissolution rates (under sink and non-sink conditions) as well as solubility studies were also examined. Serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were considered to evaluate the pharmacological efficiency of prepared SDs. According to our findings, the drug crystallinity was reduced and the drug dissolution characteristics were improved in the prepared SDs. In vivo studies revealed that oral administration of ATV (3mg/kg/day) in the SD form (ASDT) for 14days along with high fat diet (HFD) to the hypercholesterolemic rats led to a significant decline (P<0.05) in serum level of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Moreover, ASDT exhibited more beneficial effects on the liver steatosis compared to ATV physical mixture (APMT) and hyperlipidemic control (HC) groups. In the present study, it was concluded that the SDs of ATV with improved physicochemical characteristics provided an increased therapeutic potential for management of hyperlipidemia compared to the corresponding physical mixtures (PMs).

In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases

Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa .

Physical–chemical properties of furosemide nanocrystals developed using rotation revolution mixer

Recently, several approaches have been reported to improve the dissolution rate and bioavailability of furosemide, a class IV drug. However, to the best of our knowledge, none of them proposed nanocrystals. In the last decade, nanocrystals successfully addressed solubility issues by increasing surface area and saturation solubility, both leading to an increase in the dissolution rate of poor water soluble drugs. The preparation of furosemide nanocrystals was by a rotation revolution mixer method. Size distribution and morphology were performed using laser diffraction and scanning electron microscopy, respectively. In addition, differential scanning calorimetry, thermogravimetry, X-ray powder diffraction (XRD) and low frequency shift-Raman spectroscopy allowed investigating the thermal properties and crystalline state. Solubility saturation and intrinsic dissolution rate (IDR) studies were conducted. The thermal analysis revealed lower melting range for the nanocrystals comparing to furosemide. Moreover, a slight crystalline structure change to the amorphous state was observed by XRD and confirmed by low frequency shift Raman. The particle size was reduced to 231 nm with a polydispersity index of 0.232, a 30-fold reduction from the original powder. Finally, the saturation solubility and IDR showed a significant increase. Furosemide nanocrystals showed potential for development of innovative formulations as an alternative to the commercial products.

Enhanced Dissolution Rate of Dronedarone Hydrochloride via Preparation of Solid Dispersion using Vinylpyrrolidone‐Vinyl Acetate Copolymer (Kollidone® VA 64)

Solid dispersion (SD) systems have been widely used to increase the dissolution rate and oral absorption of poorly water‐soluble compounds. In order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a recent antiarrhythmic agent, SDs of DRN were formulated using conventional solvent evaporation method with amorphous polymers including hydroxypropyl methyl cellulose (HPMC), poly(vinyl pyrrolidone) (PVP), and vinylpyrrolidone‐vinyl acetate copolymer (VA64). The prepared SDs were characterized in terms of drug crystallinity, morphology, and in vitro dissolution profile in aqueous medium. The physical characterization using differential scanning calorimetry and X‐ray powder diffraction revealed that the active compound was molecularly dispersed in all polymeric carriers tested, in a stable amorphous form in drug to polymer ratios ranging from 1:0.5 to 1:2. The dissolution rates of DRN in all SDs were much higher than those from the corresponding physical mixture and drug powder alone. In particular, the greatest dissolution enhancement was obtained from the VA64‐based SD in a drug to polymer weight ratio of 1:1, achieving almost complete drug release after 120 min at pH 1.2. Thus, VA64‐based SD with higher drug dissolution rate along with a simple preparation process is suggested as an alternative for the oral formulation of the benzofuran derivative.

Ternary Inclusion Complex of Paliperidone with β-Cyclodextrin and Hydrophilic Polymer for Solubility and Dissolution Enhancement

The present study was aimed to improve aqueous solubility and dissolution behavior of a poorly water-soluble antipsychotic drug, Paliperidone (PLDN), through the formation of inclusion complexes with beta-cyclodextrin (β-CD). The effect of water soluble polymer on the complexation efficiency and solubilizing ability of β-CD was investigated using Kollidon-30 (KDN) as a ternary component. The binary complex of PLDN: β-CD was prepared by co-precipitation method in 1:1 molar ratio and ternary complex was prepared analogously to the binary complex containing 0.3% of KDN. The solid state characterization of the complexes was carried out using DSC, FTIR, XRPD, and SEM studies. The phase solubility study carried out according to the Higuchi and Connors method revealed an increase in complexation efficiency of β-CD due to addition of KDN. Saturation solubility and in vitro dissolution studies of complexes showed that the aqueous solubility and dissolution rate of drug were improved substantially compared to drug alone. The ternary complex resulted more solubility enhancement and drug release compared to binary complexes. In conclusion, the addition of KDN to the binary system of PLDN:β-CD has a synergistic effect on the solubility enhancement ability of β-CD. Hence, ternary complexation can be used as a novel approach for solubility enhancement of PLDN.

Development of a Sustained Release Solid Dispersion Using Swellable Polymer by Melting Method.

This study is to design a sustained release solid dispersion using swellable polymer by melting method. Polyethylene glycol 6000 (PEG 6000) and hydroxypropyl methylcellulose 4000 (HPMC 4000) were used in solid dispersion for not only enhancing drug dissolution rate but also sustaining drug release. HPMC 4000 is a common swellable polymer in matrix sustained release dosage form, but could not be used in preparation of solid dispersion by melting method. However, the current study utilized the swelling capability of HPMC 4000 accompanied by the common carrier PEG 6000 in solid dispersion to accomplish the goal. While PEG 6000 acted as a releasing stimulant carrier and provided an environment to facilitate the swelling of HPMC 4000, this swellable polymer could act as a rate-controlling agent. This greatly assisted the dissolution enhancement by changing the crystalline structure of drug to more amorphous form and creating a molecular interaction. These results suggested that this useful technique can be applied in designing a sustained release solid dispersion with many advantages.

The effect of drug and EUDRAGIT® S 100 miscibility in solid dispersions on the drug and polymer dissolution rate

Amorphous solid dispersions of phenytoin (diphenylhydantoin: DPH) and glibenclamide (GBM) with Eudragit® S 100 (S100) were prepared by a spray-drying. At low drug loading ratios, DPH dissolved simultaneously with S100. However, at high drug loading ratios the DPH dissolution rates were significantly reduced in comparison with those of S100 because of the rapid crystallization of DPH during the dissolution test. All of the DPH molecules in the low drug loading spray-dried sample (SPD) intimately interacted with the S100 matrix. In the SPDs with high drug loadings, only some of the DPH molecules interacted with the S100 matrix, while the excess DPH formed DPH-rich domains. When these domains contacted the water during the dissolution test, the amorphous DPH were more easily transformed into a crystalline form. In contrast to the solid dispersion of DPH/S100, that of GBM/S100 showed the simultaneous dissolution independent of the drug loading ratio. GBM was retained in an amorphous state during the dissolution test even at high drug loadings, although GBM-rich domains were formed. The miscibility at the molecular level as well as the stability of the amorphous state of drug are crucial factors to enhance the drug dissolution rate by the simultaneous dissolution with the polymer.

Preparation of polymeric fenofibrate formulations with accelerated drug release: Solvent evaporation versus co-grinding

Polymeric fenofibrate-loaded films and particles aiming at improved dissolution of this poorly water-soluble drug were prepared by solvent evaporation or co-grinding. HPMC, PVP and PEG of various molecular weights were studied. In the case of HPMC, thin films were obtained when using the solvent evaporation method, whereas in all other cases particles were obtained. Interestingly, not only the type of polymer, but also the preparation method had a substantial impact on system performance and this in a not straightforward manner: For HPMC and PVP, solvent evaporation was much more efficient than co-grinding, whereas the opposite was observed with PEG. Fenofibrate was molecularly dispersed in HPMC and PVP, whereas it was partially dissolved and partially dispersed in the form of small crystals in PEG, irrespective of the type of preparation technique. Differences in the particle size could explain why drug release was faster from PVP-based systems prepared by solvent evaporation compared to co-grinding, and why the opposite was true in the case of PEG. For HPMC, differences in system homogeneity could explain the effects of the type of preparation method. Importantly, the drug dissolution rate and extent could be substantially increased, while assuring stability during at least 3 months open storage.

High shear mixing of lactose and salmeterol xinafoate dry powder blends: Biopharmaceutic and aerodynamic performances

This work aimed to investigate the effect of a high shear mixer on the biopharmaceutics and aerodynamic performances of salmeterol xinafoate/lactose blends for inhalation. The influence of mixing energy during blending on powder bulk properties, aerosolisation and in vitro dissolution rate of drug was studied. There was a clear dependence of the blends bulk characteristics on the mixing rate and time that affected the emitted dose. The fine particle dose or respirable fraction of salmeterol xinafoate was favored by the mixing intensity leading to the disaggregation of the drug particles. An important dependence of the extra-fine drug particles on the mixing conditions was determined. The effective dispersion on the carrier particles of the salmeterol xinafoate improved the dissolution rate of the drug from the blend. This was due to the drug particle size distribution in the blend. When the fine particle dose of different blends was dissolved, no differences among the dissolution rates were observed.

Preparation and characterization of simvastatin nanoparticles using rapid expansion of supercritical solution (RESS) with trifluoromethane

Simvastatin is a drug which is widely used in the treatment of hypercholesterolemia, but it is practically insoluble in water and is not well absorbed via gastrointestinal tract. Therefore, introducing effective methods to improve its dissolution rate that may result in increased bioavailability is very important. Particle size reduction is one of the physical methods which are used to improve the dissolution rate of drugs in aqueous media. Amongst the several methods which have been used for particle size reduction, the use of supercritical fluid technology has some special advantages.In this study, the simvastatin nanoparticles (47nm), were formed using supercritical trifluoromethane and showed a significant improvement in terms of dissolution rate.The effects of extraction temperature and pressure and spray distance on particle size were analyzed. Characterization tests included X-ray diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS).Response surface methodology (RSM) was used for experimental design and process optimization and it was found that the best results can be obtained at 10MPa, 50°C, and 7cm.

Can crystal engineering be as beneficial as micronisation and overcome its pitfalls?: A case study with cilostazol

Improvement in dissolution of the drugs having poor solubility is a challenge in pharmaceutical industry. Micronization is one technique, employed for dissolution enhancement of cilostazol, a BCS class II drug. However, the obtained micronized drug possesses poor flowability. The aim of this study was to improve the dissolution rate and flow properties of cilostazol by crystal engineering, using habit modification method and compare with micronized cilostazol bulk drug. Simulation studies were performed to predict the effect of solvents on cilostazol crystal habit. Cilostazol crystals with different habits were prepared by solvent:anti-solvent crystallization technique. SEM, FTIR, DSC, TGA and PXRD were used for solid state characterization. The results revealed that cilostazol re-crystallized from methanol–hexane system were hexagonal and ethanol–hexane system gave rods. Cilostazol engineered habits showed increased dissolution rate than unprocessed drug but similar dissolution rate when compared to micronized cilostazol. Micronized cilostazol showed a dissolution efficiency of 75.58% where as cilostazol recrystallized from methanol–hexane and ethanol–hexane systems resulted in a dissolution efficiency of 72.63% and 68.63%, respectively. In addition, crystal engineering resulted in improved flow properties of re-crystallized habits when compared to micronized form of the drug. In conclusion, crystal engineering by habit modification show potential for dissolution enhancement with an added advantage of improved flow properties over micronization technique, for poorly soluble drugs like cilostazol.

Inclusion Complexes of Hydroxy Propyl-β-Cyclodextrin and Paliperidone: Preparation and Characterization.

In the present investigation, an attempt has been made to improve aqueous solubility of a BCS class II drug by making an inclusion complex with Hydroxypropyl-β-cyclodextrin (HP-β-CD). Paliperidone (PALI) was selected as a model drug for the study. It is practically insoluble in water with low oral bioavailability. It is a major active metabolite of risperidone approved for the treatment of schizophrenia in adults. The inclusion complexes were prepared in 1:1 (PALI: HP-β-CD) molar ratio. Phase solubility studies were performed according to Higuchi Connors method to determine the optimum conditions for the complexation. The prepared solid inclusion complexes were characterized by Differential Scanning Calorimetry (DSC), Fourier- Transform Infrared Spectroscopy (FT-IR), Powder X-ray Diffractometry (PXRD), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance Spectroscopy ((1)H-NMR). Dissolution study was performed using USP apparatus II in phosphate buffer, pH 6.8 (37 ± 0.5°C). The solid state characterization studies confirmed the formation of inclusion complex between PALI and HP-β-CD. The aqueous solubility and in-vitro dissolution study showed that the solubility and dissolution rate of drug were considerably improved by complexation with HP-β-CD with respect to the drug alone. The enhanced solubility and dissolution may help to improve in-vivo performance of PALI. Thus, the binary complexation of PALI with HP-β-CD can be used as an approach for its solubility enhancement.