Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract

Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.     

pH-independent dissolution enhancement for multiple poorly water-soluble drugs by nano-sized solid dispersions based on hydrophobic–hydrophilic conjugates

The objective of this study was to achieve an optimal formulation of hydrophilic–hydrophobic conjugates for nano-sized solid dispersions (SDs) with enhanced dissolution of multiple drugs in different gastrointestinal (GI) tract environments. A new conjugate powder with an optimized process was used to fabricate SDs that contained three poorly water-soluble drugs that were also poorly soluble in different dissolution media. The self-assembled nanoparticle formation, drug crystallinity and SD molecular interactions were investigated by measuring the particle size during dissolution testing and physicochemical property analysis (powder X-ray diffraction and Fourier transform infrared spectroscopy). Drug release studies indicated that SD containing conjugated powder significantly improved the dissolution rates of these poorly water-soluble drugs in the GI tract. In addition, particle size analysis showed nano-sized particles in the dissolution media in the early stage with a tendency to reduce smaller particles over time. Physicochemical characterizations demonstrated almost amorphous drug states and hydrogen bonding interactions between the drugs and conjugates in the SD. This study optimized a promising material for SD, and the material was shown to have a promising performance under various pH medium conditions with poorly water-soluble drugs.     

Use of highly compressible Ceolus™ microcrystalline cellulose for improved dosage form properties containing a hydrophilic solid dispersion

The development of amorphous solid dispersions containing poorly soluble drug substances has been well-documented; however, little attention has been given to the development of the finished dosage form. The objective of this study was to investigate the use of Ceolus(?) microcrystalline cellulose, a highly compressible excipient, for the production of rapidly disintegrating tablets containing a hydrophilic solid dispersion of a poorly soluble drug, indomethacin. Solid dispersions of indomethacin and Kollidon(?) VA64 were prepared by hot melt extrusion and characterized for amorphous nature. Milled dispersion particles at 500 mg/g drug loading were shown to be amorphous by differential scanning calorimetry and provided rapid dissolution in sink conditions. Physical characterization of the milled extrudate showed that the particle size of the intermediate was comparable with Ceolus(?) PH-102 and larger than the high compressibility grades of microcrystalline cellulose selected for the trial (Ceolus(?) KG-802, Ceolus(?) UF-711). Preliminary tableting trials showed that dissolution performance was significantly reduced for formulations at dispersion loadings in excess of 50%. Using a mixture design of experiments (DOE), the levels of PH-102, KG-802, UF-711, and PH-301 were optimized. Trials revealed a synergistic relationship between conventional grades (PH-102 and PH-301) and highly compressible grades (KG-802 and UF-711) leading to improved compression characteristics and more rapid dissolution rates. The formulation and resulting compressibility were also shown to have an impact on in vitro supersaturation indicating tablet formulation could impact oral bioavailability. Through the use of highly compressible microcrystalline cellulose grades such as Ceolus(?) KG-802 and UF-711, it may be possible to maximize the bioavailability benefit of amorphous solid dispersions administered as tablet dosage forms.     

Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions

This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15?min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500?nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5?µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.     

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD,HSDSC and Raman microscopy

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials^® to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.     

Production of advanced solid dispersions for enhanced bioavailability of itraconazole using KinetiSol® Dispersing

Objectives: To investigate the ability of KinetiSol® Dispersing to prepare amorphous solid dispersions of itraconazole using concentration-enhancing polymers. Methods: Concentration-enhancing nature of several cellulosic polymers (HPMC, hypromellose acetate succinate) was studied using a modified in vitro dissolution test. Solid dispersions were prepared by KinetiSol® Dispersing and characterized for solid-state properties using X-ray diffraction and differential scanning calorimetry. Potency and release characteristics were also assessed by high-performance liquid chromatography. Oral bioavailability of lead formulations was also assessed in animal models. Results: Screening studies demonstrated superior concentration-enhancing performance from the hypromellose acetate succinate polymer class. Data showed that stabilization was related to molecular weight and the degree of hydrophobic substitution on the polymer such that HF > MF ≈ LF, indicating that stabilization was achieved through a combination of steric hindrance and hydrophobic interaction, supplemented by the amphiphilic nature and ionization state of the polymer. Solid dispersions exhibited amorphous solid-state behavior and provided neutral media supersaturation using a surfactant-free pH change method. Rank-order behavior was such that LF > MF > HF. Addition of Carbopol 974P increased acidic media dissolution, while providing a lower magnitude of supersaturation in neutral media because of swelling of the high viscosity gel. In vivo results for both lead compositions displayed erratic absorption was attributed to the variability of gastrointestinal pH in the animals. Conclusions: These results showed that production of amorphous solid dispersions containing concentration-enhancing polymers through KinetiSol® Dispersing can provide improved oral bioavailability; however, additional formulation techniques must be developed to minimize variability associated with natural variations in subject gastrointestinal physiology.     

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials(?) to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.     

Physical Characterization and Dissolution Properties of Verapamil. HCI Coprecipitates

Verapamil hydrochloride coprecipitates were prepared using solvent-evaporation technique. Ethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose phtalate HP 55 were used as polymers. The solid dispersions obtained were grounded and sieved to prepare solid dispersion granules. The dissolution behavior of solid dispersion granules was studied using buffer solutions with pH 1.5; 6.8 and half-change method during 24 hours. The drug release rate was found to be dependent on the ratio of the polymers in coprecipitates. In order to understand the drug release mechanism better, the release data were tested assuming common kinetic models. The best fit kinetic model was diffusion model and the dissolution rate constants calculated using Higuchi equation, demonstrated that dissolution rate increased with increasing the ratio of HPMCP HP 55 in coprecipitates. Physical characterization was made using X-ray diffractometry, IR spectrophotometry and DTA studies. Prepared coprecipitates were X-ray amorphous. Also, after nine months real time studies they remain amorphous, with no changes in their IR spectra and DTA curves. The dissolution rate of the test dispersions showed no significant changes during the stability studies, reflecting the stability of X-ray amorphous drug phase.     

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T_g) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T_g from the predicted values calculated using the Couchman–Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.     

Dissolution, Bioavailability and Ulcerogenic Studies on Solid Dispersions of Indomethacin in Water Soluble Cellulose Polymers

The dissolution rate, bioavailability and ulcerogenic activity of indomethacin dispersed in water soluble cellulose polymers was investigated. Solid dispersions of indomethacin in hydroxypropyl cellulose-SL (HPC-SL), hydroxypropylmethyl cellulose (HPMC) and hydroxyethyl cellulose (HEC) were prepared by common solvent method with a view to improve its dissolution and absorption characteristics. The dispersions were evaluated by X-ray diffraction, TLC, IR, dissolution rate, bioavailability and ulcerogenic studies. TLC and IR studies indicated no interaction between indomethacin and carriers. Indomethacin in the dispersions was found to be in amorphous form. Marked increase in the dissolution rate and efficiency of indomethacin was observed in the case of solid dispersions. HPC-SL gave the highest dissolution improvement. A 30-fold increase in dissolution was observed with indomethacin-HPC-SL (9:1) dispersion.

In vivo studies in human subjects showed a significant increase in absorption rate (k_a) and serum levels of indomethacin with solid dispersions when compared to indomethacin alone. However, the extent of bioavailabilty was the same with both indomethacin and its solid dispersions. About 70-80 per cent reduction in ulcerogenic activity was observed with solid dispersions and the dispersions were found to have negligible ulcerogenic activity.     

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.     

An attempt to stabilize nilvadipine solid dispersion by the use of ternary systems

Firstly, we investigated the physical stability of nilvadipine (NIL)/crospovidone (cl-PVP) solid dispersion during storage (40°C, 75% relative humidity) with powder x-ray diffraction, differential scanning calorimetry (DSC) and dissolution test. These studies indicated that recrystallization occurred during storage and that the dissolution of NIL greatly decreased, compared with that of the initial finding. Secondly, to improve the amorphous form physical stability of NIL, methylcellulose (MC) was added to NIL/cl-PVP solid dispersions as a dispersion carrier and NIL/cl-PVP/MC ternary solid dispersion systems were obtained by the solvent method. Powder x-ray diffraction and DSC studies indicated that the amorphous form physical stability of NIL clearly improved in the NIL/cl-PVP/MC solid dispersion systems during storage. Moreover, the dissolution properties of NIL/cl-PVP/MC solid dispersion systems were characterized by cl-PVP markedly enhancing the dissolution of NIL and MC inhibiting the change of the dissolution of NIL during storage. Finally, we obtained an ideal solid dispersion that was accompanied by a consistently higher rate of dissolution.     

Dissolution rate enhancement,in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions.     

Preparation,Characterization, and Dissolution Studies of Ibuprofen Solid Dispersions Using Polyethylene Glycol (PEG), Talc,and PEG-Talc as Dispersion Carriers

Abstract

Solid dispersions of ibuprofen (IBF) were prepared by solvent evaporation method using polyethylene glycol 10000 (PEG), talc, and PEG-talc as dispersion carriers. The drug-carrier(s) interactions in the solid state were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and x-ray diffraction analysis. Interactions in the solution were studied by performing dissolution experiments. No important and well-defined chemical interaction was found between the ingredients. The increase in the IBF dissolution rate from the solid dispersions with the carriers used in this study could be attributed to several factors such as improved wettability, local solubilization, and drug particle size reduction.     

Nimesulide-modified gum karaya solid mixtures: preparation, characterization, and formulation development

Solid mixtures of nimesulide (NS) and modified gum karaya (MGK) were prepared to improve the dissolution rate of NS. The effect of drug-carrier ratio on dissolution rate of NS was investigated by preparing the solid mixtures of different ratios by cogrinding method. Solid mixtures were also prepared by physical mixing, kneading, and solid dispersion techniques to study the influence of method of preparation. Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and equilibrium solubility studies were performed to explain the results of in vitro dissolution rate studies. It was clearly evident from the results that the NS dissolution rate was dependent on the concentration of MGK in the solid mixtures, and optimum weight ratio was found to be 1:4 (NS:MGK). Though the dissolution rate of NS from all solid mixtures prepared by different methods improved significantly, maximum improvement in dissolution rate was observed with solid dispersions. The order of methods basing on their effect on dissolution efficiency is solid dispersion > kneading > cogrinding > physical mixing > pure NS. Tablets of pure drug and solid mixtures (1:4 w/w, NS:MGK) were prepared. Though the best results from the dissolution test were obtained for the tablets containing solid dispersions, tablets containing cogrinding mixture were found to be suitable, from a practical point of view, for commercialization.     

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus

Abstract

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (Soluplus^®) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus^® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40?°C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug–polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus^®, when protected from moisture.     

Preparation of Budesonide-Poly (Ethylene Oxide) Solid Dispersions Using Supercritical Fluid Technology

The purpose of this study was to investigate the possibility of preparing solid dispersions of the poorly soluble budesonide by supercritical fluid (SCF) technique, using poly (ethylene oxide) (PEO) as a hydrophilic carrier. The budesonide-PEO solid dispersions were prepared, using supercritical carbon dioxide (SC CO₂) as the processing medium, and characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), solubility test and dissolution test in order to understand the influence of the SCF process on the physical status of the drug. The endothermic peak of budesonide in the SCF-treated mixtures was significantly reduced, indicating that budesonide was in amorphous form inside the carrier system. This was further confirmed by SEM and PXRD studies. The enhanced dissolution rates of budesonide were observed from SCF-treated budesonide-PEO mixtures. The amorphous characteristic of the budesonide, the better mixing of drug and PEO powders in the presence of SC CO₂, together with the improved wettability of the drug in PEO, produced a remarkable enhancement of the in vitro drug dissolution rate. Thus, budesonide-PEO solid dispersions with enhanced dissolution rate can be prepared using organic solvent-free SCF process.     

Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration

The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1?mg tacrolimus for sublingual application. First, solid dispersions containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol(?) and carriers (inulin 1.8?kDa and 4?kDa, and polyvinylpyrrolidone (PVP) K30) were prepared by freeze drying. Subsequently, a tablet formulation composed of a mixture of the solid dispersions, Ac-Di-Sol(?), mannitol, Avicel(?) PH-101 and sodium stearyl fumarate was optimized concerning drug load in the solid dispersions and the type of carrier. Tablet weight was kept constant at 75?mg by adjusting the amount of Avicel(?) PH-101. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) results indicated the absence of the drug in the crystalline state, which was confirmed by the scanning electron microscopy (SEM). These results suggest that tacrolimus incorporated in all of the solid dispersions was fully amorphous. Dissolution of the tablets containing solid dispersions with a low drug load highly depends on the type of carrier and increased in the order: PVP K30 < inulin 4?kDa < inulin 1.8?kDa. Solid dispersions with a drug load of 10% w/w incorporated in the carriers yielded optimal formulations. In addition, the physicochemical characteristics and the dissolution behavior of the tablet formulation containing inulin 1.8 kDa-based solid dispersions with a drug load of 10% w/w did not change after storage at 20°C/45%RH for 6 months indicating excellent storage stability.     

Influence of alkalizers on dissolution properties of telmisartan in solid dispersions prepared by cogrinding

The amorphous solid dispersions of telmisartan salts were prepared by cogrinding, in presence of alkalizers and polyvinylpyrrolidone (PVP_k30). Five alkalizers in this study were MgO, Na₂CO₃, K₂CO₃, NaHCO₃ and meglumine. In soft mode using a roll mill, the drug could not form salt with MgO or NaHCO₃, whereas partial drug had been transformed into salt with carbonates or meglumine. Under cogrinding, the organic base meglumine was easier to react with telmisartan than other two carbonates. For getting good dissolution performance, the drug had to be transformed into salt completely. A high intensity oscillating mill was applied for producing telmisartan meglumine salt. Multi-instrumental characterizations attested the formation of amorphous salt by high mechanical process, involving dissolution test, fourier transform infrared spectroscopy and powder X-ray diffractometry. It was evident that solid dispersions of telmisartan meglumine salt significantly increased the drug dissolution rate in intestinal fluid.     

Investigation of dissolution enhancement of itraconazole by solid dispersion in superdisintegrants

Solid dispersions of itraconazole (ITR) in lactose, microcrystalline cellulose (MCC), and three superdisintegrants (Primogel, Kollidon CL, and Ac-Di-Sol) and their formulation into tablets were investigated with an objective of enhancing the dissolution rate of ITR from tablet formulations. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize the dispersions. A marked enhancement in the dissolution rate of ITR was observed with all the excipients. The order for the excipients to enhance the dissolution rate was Ac-Di-Sol > Kollidon CL > Primogel > MCC > lactose. Solid dispersions in superdisintegrants gave much higher rates of dissolution than the dispersions in other excipients. Ac-Di-Sol gave the most improvement (28-fold) in the dissolution rate of ITR at a 1:1 drug:excipient ratio. Solid dispersions in superdisintegrants could be formulated into tablets. These tablets, apart from fulfilling all official and other specifications, exhibited higher rates of dissolution and dissolution efficiency (DE) values. XRD indicated the presence of ITR in amorphous form in the dispersions. DSC indicated a weak interaction between ITR and the excipients. Micronization and conversion of the drug into the amorphous form and the fast disintegrating and dispersing action of the superdisintegrants contribute to the enhancement of the dissolution rate of ITR from its solid dispersions in superdisintegrants and their corresponding tablet formulations.