Faster Dissolution Rate Research Articles

Novel redispersible nanosuspensions stabilized by co-processed nanocrystalline cellulose-sodium carboxymethyl starch for enhancing dissolution and oral bioavailability of baicalin.

BackgroundTo improve the dissolution and bioavailability of poorly soluble drugs, novel nanosuspensions using co-processed nanocrystalline cellulose–sodium carboxymethyl starch (NCCS) as a synergetic stabilizer were first designed.MethodsCo-processed NCCS was prepared by means of homogenization. Poorly soluble baicalin (BCA) was used as a model drug. BCA nanosuspension (BCA-NS/NCCS) using co-processed NCCS as a dispersant was prepared via homogenization and further converted into the dried BCA nanosuspension particle (BCA-NP/NCCS) via spray drying. The influence of NCCS on the dispersion efficiency of BCA-NS/NCCS was investigated. Morphology and crystal characteristic of NCCS and BCA-NP were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of NCCS as a stabilizer for BCA-NS/NCCS and BCA-NP.ResultsThe optimum 50% concentration of NCCS (nanocrystalline cellulose [NCC]:sodium carboxymethyl starch [SCS]=60:40) could be mostly beneficial for formation and stability of BCA-NS/NCCS. NCCS could completely prevent aggregation of BCA-NP during spray drying and enhance the redispersibility as well as dissolution of spray-dried BCA-NP, which might be attributed to “brick–concrete”-based barrier effect of NCCS and the swelling capacity of superdisintegrant SCS. The crystal state of NCC and BCA presented in BCA-NP/NCCS remained unchanged during the homogenization. The BCA-NP/NCCS exhibited a fast dissolution rate and significantly enhanced bioavailability of BCA. The AUC(0–∞) of the BCA-NP/NCCS (8,773.38±718.18 µg/L·h) was 2.01 times (P<0.05) as high as that of the crude BCA (4,354.61±451.28 µg/L·h).ConclusionThis study demonstrated that novel surfactant-free nanosuspensions could be prepared using co-processed NCCS as a synergetic stabilizer and also provided a feasible strategy to improve the dissolution and oral bioavailability of poorly soluble drug.

Preparation and Characterization of Taxifolin Form II by Antisolvent Recrystallization

AbstractTo improve the aqueous solubility and dissolution rate of taxifolin, taxifolin form II was successfully prepared through antisolvent recrystallization, in which 1‐butyl‐3‐methylimidazolium tetrafluoroborate and dichloromethane were used as solvent and antisolvent, respectively. The properties of taxifolin form II were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X‐ray diffraction, differential scanning calorimetry, solid‐state NMR spectroscopy, the dissolving capability test, and the bioavailability test. The chemical structure of taxifolin form II was not changed, but its morphology and crystalline structure changed during the recrystallization process. Moreover, taxifolin form II showed higher solubility, faster dissolution rate, and better bioavailability than taxifolin form I.

Whey proteins as stabilizers in amorphous solid dispersions

Whey proteins are extensively used as nutritional supplements but have so far not been investigated as co-formers for amorphous solid dispersions (ASD) to enhance the solubility and dissolution rate of poorly water soluble drugs. In this study, whey protein isolate (WPI) and whey protein hydrolysate (WPH) were each mixed with three poorly water soluble drugs (indomethacin: IND, carvedilol: CAR and furosemide: FUR) and prepared as ASDs at 50% (w/w) drug loading using vibrational ball milling. Subsequently, solid state characteristics, dissolution rate and physical stability of the obtained samples were analyzed. All ASDs showed a significant increase in their glass transition temperatures, as well as faster dissolution rates and higher apparent solubilities compared to both the respective pure crystalline and amorphous drugs. The saturation solubility of the drugs was increased in the presence of the whey proteins, and the investigated ASDs showed supersaturation by attaining higher drug concentrations compared to the respective saturation solubilities. Upon storage, ASDs containing IND were found to be physically stable for at least 27 months, whereas, ASDs containing CAR or FUR were stable for about 8 months and 17 months, respectively. This was a tremendous increase in physical stability compared to the pure amorphous drugs which recrystallized within less than one week. Overall, WPI and WPH proved to be promising co-formers and amorphous stabilizers in ASD formulations.

The Interface Reaction between Titanium and Iron-Nickel alloys

AbstractThe reaction zones between pure titanium and iron-nickel and pure nickel at 1173 K have been characterized. Two alloys with different initial composition were analyzed. When Ni80Fe20 is used the layer sequence at the reaction interface is: Ni80Fe20 → Ni3Ti → NiTi → NiTi2 →Ti, while for Ni48Fe52 the sequence is: Ni48Fe52 → Ni3Ti → TiFe2 → TiFe → NiTi2 → Ti. The difference is in formation of NiTi, TiFe2 and TiFe phases. The reaction zone remains very thin independently of time due to the fast dissolution rate of Ti in the alloy. The two different elementary chemical interaction processes have been identified in this article, namely the growth of the reaction layers by solid state diffusion and chemical conversion of the compounds by reaction-diffusion in the solid state. The mathematical description combining these processes is presented for description of the diffusion path generated during diffusion process.

Development of fast-release piroxicam/polyethylene glycol capsules by solid dispersion and curing using full factorial design

Purpose: To develop fast-release piroxicam (PRX) capsules by solid dispersion with polyethylene glycol (PEG) using melting and curing in a heated coating pan.Methods: A full factorial design was conducted to investigate the main and interaction effects of molecular weight (4000 - 8000 Da) and amount (10 - 30 mg PEG to 10 mg PRX) on the dissolution rate of PRX. Temperature (50 - 70 °C) and duration of the curing process (15 - 45 min) were also systematically selected by factorial design.Results: The molecular weight and amount of PEG significantly impacted on the dissolution rate of PRX (p = 0.04 and 0.01, respectively), while temperature and duration of the curing process were not significant effects (p = 0.10 and 0.17, respectively). Based on the results, a fast dissolution rate and burst release of PRX was obtained from capsules formulated by PRX/PEG 8000 (1:3 weight ratio) as a solid dispersion compared to the physical mixture and free drug. Furthermore, this capsule was in the acceptance range for the labeled amount, weight variation and disintegration time.Conclusion: PRX/PEG melted solid dispersion capsule may be a suitable immediate release drug delivery system with improved dissolution rate and increased drug absorption.Keywords: Capsules, Solid dispersion, Piroxicam, Polyethylene glycol, Fast release, Full factorial design

FORMULATION DEVELOPMENT AND CHARACTERISATION OF MECLIZINE HYDROCHLORIDE FAST DISSOLVING TABLETS USING SOLID DISPERSION TECHNIQUE

Objective: The aim of the present investigation was to design and evaluate fast dissolving tablet (FDT) for the oral delivery containing solid dispersion of meclizine (MCZ) hydrochloride, an antiemetic drug.Methods: The solubility of meclizine was increased by preparing solid dispersions using mannitol as a carrier by fusion method. The prepared solid dispersion, was subjected for in vitro drug release, percent practical yield, drug content, infrared spectroscopy (IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM). Optimized solid dispersion was incorporated to prepare fast dissolving tablets. Preformulation studies were carried out on tablet blends. The prepared solid dispersion, as well as pure drug fast dissolving tablets, was evaluated for drug content, weight variation, hardness, friability, in vitro drug release, wetting time, disintegration time, water absorption ratio, in vitro dispersion time.Results: Meclizine pure drug, solid dispersions formulations SD1, SD3 and SD5 showed 12.8, 31.68, 38.92 and 53.28% cumulative drug release in phosphate buffer pH 6.8 after 60 min, respectively. Thus faster dissolution rate was exhibited by the solid dispersion containing 1:5 (w/w) ratio of meclizine: mannitol. Percent cumulative drug release for control and solid dispersion tablets after 60 min in phosphate buffer pH 6.8 was 92.04 and 98.2% respectively. The release of drug meclizine from best formulation SD5 FDT was found to be faster than pure drug FDT.Conclusion: Fast dissolving tablet of optimized solid dispersion showed better in vitro dissolution result then FDT of pure drug at the end of one hour.

PREPARATION AND EVALUATION OF RAPIDLY DISSOLVING ‎TABLET OF TELMISARTAN

Objective: The aim of this work was to enhance the dissolution rate of telmisartan with the goal of developing fast disintegrating tablets (FDTs) with subsequent rapid dissolution for sublingual administration. Methods: Binary solid dispersion systems (SDS) were prepared by solvent evaporation technique for the drug with Gelucire 44/14 (formula A), polyethylene glycol 4000 (PEG4000) (formula B), Pluronic F68 (formula C), hydroxypropyl methylcellulose E5 (HPMC E5) (formula D), and finally by using sodium bicarbonate with the drug in (0.5: 1) ratio (formula E), and (1:1) ratio (formula F). These systems were evaluated for drug dissolution in addition to the physicochemical changes of the drug utilizing FTIR spectroscopy, thermal analysis, and X-ray diffraction. Results: The prepared formulations using sodium bicarbonate significantly enhanced the dissolution rate of the drug compared with those prepared using different types of polymers. The order of enhanced dissolution of the drug in the first 5 min Q5 (%) was: formula E > F > D5, where the % drug dissolved was 88.94 ± 1.31, 84.77 ± 1.1 and72.6 ± 0.81 (mean + SD) for each formula, respectively. Formula E was selected for the formulation of the rapidly dissolving tablet of telmisartan since it showed enhanced dissolution of the drug, more palatable taste in the buccal cavity, relatively inexpensive material and ease of processing compared with a solid dispersion prepared using polymer. Conclusion: Sodium bicarbonate can be utilized in the preparation of telmisartan FDT with fast dissolution rate. Conclusion: sodium bicarbonate can be utilized in the preparation of telmisartan FDT ‎with fast dissolution rate.‎

A new therapeutic avenue for bronchiectasis: Dry powder inhaler of ciprofloxacin nanoplex exhibits superior ex vivo mucus permeability and antibacterial efficacy to its native ciprofloxacin counterpart

Non-cystic fibrosis bronchiectasis (NCFB) characterized by permanent bronchial dilatation and recurrent infections has been clinically managed by long-term intermittent inhaled antibiotic therapy among other treatments. Herein we investigated dry powder inhaler (DPI) formulation of ciprofloxacin (CIP) nanoplex with mannitol/lactose as the excipient for NCFB therapy. The DPI of CIP nanoplex was evaluated against DPI of native CIP in terms of their (1) dissolution characteristics in artificial sputum medium, (2) ex vivo mucus permeability in sputum from NCFB and healthy individuals, (3) antibacterial efficacy in the presence of sputum against clinical Pseudomonas aeruginosa strains (planktonic and biofilm), and (4) cytotoxicity towards human lung epithelial cells. Despite their similarly fast dissolution rates in sputum, the DPI of CIP nanoplex exhibited superior mucus permeability to the native CIP (5–7 times higher) attributed to its built-in ability to generate highly supersaturated CIP concentration in the sputum. The superior mucus permeability led to the CIP nanoplex’s higher antibacterial efficacy (>3 log10 CFU/mL). The DPI of CIP nanoplex exhibited similar cytotoxicity towards the lung epithelial cells as the native CIP indicating its low risk of toxicity. These results established the promising potential of DPI of CIP nanoplex as a new therapeutic avenue for NCFB.

Chemical treatment for recycling of amine/epoxy composites at atmospheric pressure

The use of fiber-reinforced composites poses significant environmental problems because most end-of-life composite waste is sent to landfills, and effective recycling technologies have drawn research attention. Our previous study demonstrated that chemical treatments at atmospheric pressure – depolymerization (benzyl alcohol/K3PO4 at 200 °C) and acid digestion (acetic acid/H2O2 at 110 °C) – were both effective for dissolution of amine-cured neat epoxy. In this paper, depolymerization and acid digestion were applied to amine/epoxy composites, including composites produced from lab-made and aerospace prepregs, and commercial composite waste. Findings indicated that acid digestion was more effective for highly crosslinked amine/epoxy composites than depolymerization. Furthermore, digestion occurred via reaction steps of oxygen atom transfer to the aniline groups and then bond cleavage, resulting in recovery of near-virgin quality fibers at faster dissolution rates and lower temperatures. The relationship between epoxy functionality, fiber bed architecture, fiber reinforcement, laminate thickness and matrix dissolution rate were investigated, and key parameters affecting the dissolution rate were identified. Data showed that the major rate-limiting factor for acid digestion was the diffusion rate, rather than the chemical reaction rate. Two strategies to enhance the diffusion rate – pre-treatment and mechanical shredding – were evaluated, and both were effective. Polymer matrices in pre-treated and shredded composites were homogeneously decomposed in 1 h.

Nanostructured Ag+-substituted fluorhydroxyapatite-TiO2 coatings for enhanced bactericidal effects and osteoinductivity of Ti for biomedical applications.

BackgroundPoor mechanical properties, undesirable fast dissolution rate, and lack of antibacterial activity limit the application of hydroxyapatite (HA) as an implant coating material. To overcome these limitations, a hybrid coating of Ag+-substituted fluorhydroxyapatite and titania nanotube (TNT) was prepared.MethodsThe incorporation of silver into the HA-TiO2 hybrid coating improves its antimicrobial properties. The addition of F as a second binary element increases the structural stability of the coating. The TNT/F-and-Ag-substituted HA (FAgHA) bilayer coating on the Ti substrate was confirmed by X-ray diffraction, scanning electron microscope, energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS).ResultsThe results indicate that the FAgHA/TNT nanocomposite coating has a dense and uniform morphology with a nano-rod-like structure. The solubility measurement result shows that the substitution of F− ions into the AgHA structure has a positive effect on the dissolution resistance of HA. The adhesion strength of FAgHA/TNT has significantly increased because of the interlocking of the roughened surface with nano-rod-like particles that entered into the voids of the TiO2 nanotubes. Compared with that of the bare Ti, the corrosion current density of FAgHA/TNT-coated Ti substrate decreased from 3.71 to 0.18 μA, and its corrosion resistance increased by almost two orders of magnitude. Moreover, despite pure HA, the FAgHA killed all viable Staphylococcus aureus after 24 hours of incubation. Although the fabricated FAgHA/TNT coating is hydrophobic, it induced deposition of the typical spherical apatite when immersed in a simulated body fluid (SBF); the osteoblasts spread very well on the surface of the coating. In addition, in vitro cell culture tests demonstrated cell viability and alkaline phosphatase (ALP) similar to pure HA, which indicated good cytocompatibility. Interestingly, compared with bare Ti, FAgHA/TNT-coated Ti surface was innocent for cell vitality and even more beneficial for cell osteogenesis in vitro.ConclusionEnhancing the osseointegration and preventing infection in implants, the FAgHA/TNT-coated Ti makes implants more successful.

Potential application of a low-viscosity and high-transparency xanthan gum produced from Xanthomonas campestris CCTCC M2015714 in foods

ABSTRACTXanthan gum is commonly used as a thickener in food industry, while the usage of xanthan gum as a dietary fiber is restricted for its low additive volume. Herein, the potential use of a low-viscosity and high-transparency xanthan gum as a dietary fiber was evaluated in vitro. This new xanthan shows better transparency and faster dissolution rate than most commercial products, and its viscosity increases along with the treatment of freeze–thaw cycles at −20°C. Moreover, this new xanthan can absorb heavy metals (Pb, Cd, Cu) and retard starch digestion by glucoamylase. In summary, this new xanthan could be potentially used as a dietary fiber or fiber ingredient for preventing and treating diabetes, hyperlipemia, heavy metal poisoning, and cardiovascular diseases effectively.

Improved properties of fine active pharmaceutical ingredient powder blends and tablets at high drug loading via dry particle coating

It has been shown that dry coating cohesive active pharmaceutical ingredients (APIs) with nano-silica can improve packing and flow of their blends, facilitating high speed direct compression tableting. This paper examines the broader scope and generality of previous work by examining three fine APIs; micronized Acetaminophen (mAPAP), coarse Acetaminophen (cAPAP) and micronized Ibuprofen (mIBU), and considers dry coating with both hydrophobic or hydrophilic nano-silica to examine the effect not only on packing density and flow of their blends, but also dissolution and tensile strength of their tablets. The impact of the excipient size on blend and tablet properties are also investigated, indicating blend flow is most improved when matching API particle size with excipient particle size. In all cases where the API is dry coated, the blend packing and flow improve, so as to suggest such high drug loaded blends could enable direct compression. Using dry coated API along with finer excipients in blends lead to improved hardness of the corresponding tablets. Interestingly, dissolution profiles show dry coated API tablets generally have faster dissolution rates, regardless of silica hydrophilicity, suggesting API powder deagglomeration via nano-silica coating plays a crucial role. The most significant conclusion is that, although there are differences in properties of blends that depend on the API, hydrophobic or hydrophilic nano-silica coating, as well as large or fine excipients, in all cases, dry coating of APIs significantly improves the possibility of using the specific blend at high drug loading in direct compression tableting.

Kinetics of dissolution of sapphire in melts in the CaO–Al2O3–SiO2 system

The dissolution rate of sapphire in melts in the CAS system of varying silica activity, viscosity and degree of alumina saturation has been determined at 1600 °C and 1.5 GPa. After an initiation period of up to 1800 s, dissolution is controlled by diffusion of cations through the boundary layer adjacent to the dissolving sapphire. The dissolution rate decreases with increasing silica activity, viscosity and molar Al2O3/CaO. The calculated diffusion matrix for each solvent melt shows that CAS 1 and 9 which have molar Al2O3/CaO of 0.33 and 0.6 and dissolution rate constants of 0.65 × 10−6 and 0.59 × 10−6 m/s0.5 have similar directions and magnitudes of diffusive coupling: DCaO-Al2O3 and DAl2O3-CaO are both negative are approximately equal. The solvent with the fastest dissolution rate: CAS 4, which has a rate constant of 1.5 × 10−6 m/s0.5 and Al2O3/CaO of 0.31 has positive DCaO-Al2O3 and negative DAl2O3-CaO and the absolute values vary by a factor of 4. Although many studies show that aluminium is added to the melts via the reaction:Si4+=Al3++0.5Ca2+the compositional profiles show that this reaction is not the only one involved in accommodating the aluminium added during sapphire dissolution. Rather, aluminium is incorporated as both tetrahedrally coordinated Al charge balanced by Ca and as aluminium not charge balanced by Ca (termed Alxs). This reaction:AlIV–Ca=Alxs+CaNBOwhere CaNBO is a non-bridging oxygen associated with calcium, may involve the formation of aluminium triclusters. The shape of the compositional profiles and oxide-oxide composition paths is controlled by the aluminium addition reaction. When Alxs exceeds 2%, CaO diffusion becomes increasingly anomalous and since the bond strength of Alxs correlates with CaO/CaO + Al2O3, the presence of more than 2% Alxs leads to significantly slower dissolution than when Alxs is absent or at low concentration. Thus, dissolution is controlled by diffusion of cations through the boundary layer, but this diffusion is itself controlled by the structural modifications required by the addition of new components to the melt. Comparison of quartz dissolution rates in similar melts shows that dissolution is much faster for quartz than for sapphire and that dissolution rates show the same correlation with silica activity and viscosity. We suggest that diffusive fluxes are related to changes in melt structure and the nature of the reaction that incorporates the added component. For the slow eigendirection, SiO2 addition occurs by a single reaction whereas Al2O3 addition requires a more complex two part reaction in which Al is accommodated by charge balance with Ca until Al is in excess of that which can be charge balanced. The Alxs incorporation reaction, is slower than the Si incorporation reaction which inhibits sapphire dissolution relative to quartz in melts of the same composition.

Effect of calcium sulfate type and dosage on properties of calcium aluminate cement-based self-leveling mortar

In this paper, the influence of calcium sulfate type (α-hemihydrate, anhydrite and dihydrate) and amount (0%, 2%, 4% and 6%) on the performances of calcium aluminate cement-based self-leveling mortar (SLM) were investigated. The influence of calcium sulfate on fluidity and mechanical properties was investigated. Moreover, the impact of calcium sulfate on the hydration products, morphology and heat evolution of pastes hydrated up to 3 days were determined by using X-ray diffraction (XRD), Scanning electron microscope (SEM) and isothermal heat-conduction calorimeter. Test results revealed that SLM prepared with anhydrite exhibited the highest initial flow value (∼160 mm) and setting time and the lowest fluidity loss due to the slow dissolution rate of anhydrite compared to other calcium sulfate. In comparison to control formulation, the enhancement in flexural and compressive strength for T4 (dihydrate) was the highest and was found to be 485.71% and 437.5% respectively and hence it can be concluded that dihydrate is favorable to the early strength of SLM as compared to other SLM formulations containing α-hemihydrate and anhydrite respectively. The shrinkage compensating effect became more obvious with the increase in the amount of C$ in SLM samples. Due to the fast dissolution rate, mortar containing α-hemihydrate exhibited more expansion as compared to other calcium sulfate. SLM prepared with dihydrate showed the highest early strength due to the lowest influence on C3S hydration while the influence of α-hemihydrate was more obvious. Hence, the hydration of PC in the ternary system can be limited by increasing calcium sulfate due to the formation of ettringite. Finally, the type of calcium sulfate has an important influence on the quantity and morphology of ettringite.

Electrospun amorphous medicated nanocomposites fabricated using a Teflon-based concentric spinneret

AbstractFacile methods to improve the dissolution rate of poorly water-soluble drugs are highly sought after. In this study, a modified coaxial electrospinning process was exploited to create medicated amorphous nanocomposites, an approach characterized by the application of a Teflon-coated coaxial spinneret. The hydrophilic polymer hydroxypropyl methylcellulose and the active ingredient tamoxifen citrate (TAM) were selected as the drug carrier and model drug, respectively. Their electrospun nanocomposites showed linear morphology with the drug presented in an amorphous state. The loaded cargoes could be released from the nanocomposites simultaneously when they were placed in the dissolution media, showing faster dissolution rates than their counterparts (physical mixtures). Based on the reasonable application of the polymeric carrier, the reported protocols not only provided an approach to enhance the dissolution of poorly water-soluble drugs, but also exhibited a method to facilitate the implementation of coaxial electrospinning.

Bromine leaching as an alternative method for gold dissolution

It is known since the end of the XIX century that bromine is an excellent leaching reagent for gold but the research concerning its potential application as an alternative reagent has been relatively despised, mainly because elemental bromine is hazardous and extremely difficult to store or transport in safe conditions. We performed experimental tests in order to assess the feasibility of bromine produced in-situ, in the leaching reactor, to dissolve gold using ore samples from the unexploited Portuguese mine of Castromil. The reagents used in the production of bromine (NaBr, NaOCl and HCl) can be more safely stored than bromine. The ore sample was crushed and grinded in order to produce a particle size distribution (D80 = 0.48 mm) that would guarantee that most of the gold and electrum would be liberated in accordance with previous mineralogical studies. The following operating conditions were assessed: temperature, solid/liquid ratio, composition of the leaching reagent, stirring speed, residence time, effect of pretreatments and the addition of oxidants to the bromine solution. The highest gold dissolution (89%) was achieved with a previous roasting, although the simultaneous addition of H2O2 and FeCl3 allows for a similar recovery (80%) with much lower environmental impact. These results were achieved with the following leaching solution: 4.4 g NaBr, 30 mL NaOCl, 42 mL HCl and 28 mL H2O and with the following operating conditions: a solid/liquid ratio of 1, temperature around 95 °C, stirring speed of 450 rpm, natural reaction pH and a leaching time of 4 h. The comparison between bromine, cyanide and thiosulfate leaching for the same ore indicates that bromine is a good technical alternative for leaching this gold ore. The following advantages may be stressed: fast dissolution rate, non-toxic reagents, it does not require the use of pH regulator and can be performed with low quantities of leaching solution.

A trade-off between solubility enhancement and physical stability upon simultaneous amorphization and nanonization of curcumin in comparison to amorphization alone

The numerous health benefits of curcumin (CUR) have not been fully realized due to its low aqueous solubility, resulting in poor bioavailability. While amorphization of CUR via amorphous solid dispersion (ASD) represents a well-established CUR solubility enhancement strategy, simultaneous amorphization and nanonization of CUR via amorphous CUR nanoparticles (or nano-CUR in short) have emerged only recently as the plausibly superior alternative to ASD. Herein we examined for the first time the amorphous nano-CUR versus the ASD of CUR in terms of their (1) in vitro solubility enhancement capability and (2) long-term physical stability. The ASD of CUR was prepared by spray drying with hydroxypropylmethylcellulose (HPMC) acting as crystallization inhibitor. The amorphous nano-CUR was investigated in both its (i) aqueous suspension and (ii) dry-powder forms in which the latter was prepared by spray drying with adjuvants (i.e. HPMC, trehalose, and soy lecithin). The results showed that the amorphous nano-CUR (in both its aqueous suspension and dry-powder forms) exhibited superior solubility enhancement to the ASD of CUR attributed to its faster dissolution rates. This was despite the ASD formulation contained a larger amount of HPMC. The superior solubility enhancement, however, came at the expense of low physical stability, where the amorphous nano-CUR showed signs of transformation to crystalline after three-month accelerated storage, which was not observed with the ASD. Thus, despite its inferior solubility enhancement, the conventional ASD of CUR was found to represent the more feasible CUR solubility enhancement strategy.

Oral bioavailability enhancement of β-lapachone, a poorly soluble fast crystallizer, by cocrystal, amorphous solid dispersion, and crystalline solid dispersion

The aim of this paper was to compare the in vitro dissolution and in vivo bioavailability of three solubility enhancement technologies for β-lapachone (LPC), a poorly water soluble compound with extremely high crystallization propensity. LPC cocrystal was prepared by co-grinding LPC with resorcinol. LPC crystalline and amorphous solid dispersions (CSD and ASD) were obtained by spray drying with Poloxamer 188 and HPMC-AS, respectively. The cocrystal structure was solved by single crystal x-ray diffraction. All formulations were characterized by WAXRD, DSC, POM and SEM. USP II and intrinsic dissolution studies were used to compare the in vitro dissolution of these formulations, and a crossover dog pharmacokinetic study was used to compare their in vivo bioavailability. An 1:1 LPC-resorcinol cocrystal with higher solubility and faster dissolution rate was obtained, yet it converted to LPC crystal rapidly in solution. LPC/HPMC-AS ASD was confirmed to be amorphous and uniform, while the crystal and crystallite sizes of LPC in CSD were found to be ∼1–3 μm and around 40 nm, respectively. These formulations performed similarly during USP II dissolution, while demonstrated dramatically different oral bioavailability of ∼32%, ∼5%, and ∼1% in dogs, for CSD, co-crystal, and ASD, respectively. CSD showed the fastest intrinsic dissolution rate among the three. The three formulations showed poor IVIVC which could be due to rapid and unpredictable crystallization kinetics. Considering all the reasons, we conclude that for molecules with extremely high crystallization tendency that cannot be inhibited by any pharmaceutical excipients, size-reduction technologies such as CSD could be advantageous for oral bioavailability enhancement in vivo than technologies only generating transient but not sustained supersaturation.

Dissolution studies of Na2O-BaO-CaO-P2O5 glasses in deionized water under semi-dynamic conditions for bioactive applications

The phosphate glasses of composition Na2O-CaO-P2O5 are widely accepted glass material for biomedical applications. The glass samples with composition (26-x)Na2O-xBaO-29CaO-45P2O5 (x = 0,5,10,15) are prepared at 1100°C by melt-quenching technique. In order to reduce the fast dissolution rate, which limits their application, BaO is added by reducing Na2O composition. The dissolution studies have been carried out in deionized water under semi-dynamic conditions at 37°C for 14 days. The properties are studied based on Barium composition and time of immersion. The samples are taken out at 24 hrs. intervals to carry out weight loss and pH measurements. The rates of cation (Na+ and Ca2+) release from the glass to the solution were found out using flame photometer. The release of orthophosphate (PO43-) anions is measured by UV-Visible spectrometer using phospho-molybdenum blue method. The weight losses linearly increase with time for all the compositions. The addition of barium decreases the weight loss in deionized water. The pH of the solutions varies with dissolution of ions. The dissolution rate has been found out from the slope of the weight loss vs time graph and it decreased with increase in barium content

Upgrading of dissolution and anti-hypertensive effect of Carvedilol via two combined approaches: self-emulsification and liquisolid techniques

Objective: The aim of the study was to design a self-emulsifying drug delivery system (SEDDS) of the anti-hypertensive Carvedilol in liquid and liquisolid forms as a way to enhance its dissolution profile and anti-hypertensive effect.Methods: Solubility studies of Carvedilol in various oils, surfactants and co-surfactants were conducted, followed by the construction of pseudo-ternary phase diagrams and other in vitro assessments. The selected SEDDS formulation (S1) was adsorbed onto solid powder excipients and compressed into tablets. The resulting liquisolid tablets were evaluated under British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies in hypertensive rats.Results: Attempts of self-emulsification, droplet size, and thermodynamic stability studies showed acceptable results for the S1 formulation containing Capryol 90, Tween 20, and Transcutol HP (10:53.3:26.2%), respectively. Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with Carvedilol. The selected liquisolid tablet (LS7) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. A significantly (p < .05) fast dissolution rate was observed for both SEDDS and liquisolid formulations when compared to pure drug and marketed Carvepress®. The in vivo study of LS7 formulation revealed a rapid significant (p < .01) decrease in the mean arterial pressure (MAP) of the rats (112.72 mmHg) within the first 30 min followed by a further decline (107.22 mmHg) after 1 h when compared to Carvepress®.Conclusion: Self-emulsifying liquisolid tablets expressed rapid onset of action with enhanced anti-hypertensive effect of Carvedilol.