Faster Dissolution Rate Research Articles

A mucoadhesive biodissolvable thin film for localized and rapid delivery of lidocaine for the treatment of vestibulodynia

Vestibulodynia (VBD), an idiopathic pain disorder characterized by erythema and pain of the vulvar vestibule (the inner aspect of the labia minora and vaginal opening), is the most common cause of sexual pain for women of reproductive age. Women also feel discomfort with contact with clothing and tampon use. As most women with this disorder only have pain with provocation of the tissue, topical anesthetics applied to the vestibule are the current first line treatment for temporary pain relief. Treatment options are limited due to anatomical constraints of the vestibular region, poor drug retention time, imprecise dosing, leakage, and overall product messiness. In this study we report a novel approach to treatment of VBD using thin film designed to fit the vulvar vestibule and deliver lidocaine locally. Two use cases for VBD treatment were identified 1) rapid drug release (<5 min), for use prior to intercourse and 2) long-acting release (≥120 min) for prolonged use and relief throughout the day. Cellulose-based mucoadhesive thin films were fabricated using a solvent casting method. Three polymers including hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), and hydroxypropylmethycellulose (HMPC), were selected owing to their biocompatibility and ideal properties for film casting. Films casted with HEC, HPC, and HPMC exhibited mucoadhesive properties relative to a control, with the highest mucoadhesive force recorded for films casted with HPC. Effect of media volume, pH, presence of mucin and presence of drug on film dissolution rates were investigated. Dissolution rates were independent of media volume, media pH or drug presence, whereas faster dissolution rates were obtained for all films in presence of mucin. In vitro lidocaine release kinetics were influenced by polymer type, percent drug loading and film casting thickness. Lidocaine release was based on a diffusion mechanism rather than through film dissolution and faster release (∼5 min) was observed for HEC films compared HPC films (∼120 min). Higher drug loading and film thickness resulted in slower and more prolonged release kinetics of lidocaine. All films were biocompatible and exhibited good mechanical properties. Two film formulations (9% w/w HPC with 12% w/w LHC, 5% w/w HEC with 6% w/w LHC) were optimized to meet the two use case scenarios for VBD treatment and moved into in vivo testing. In vivo testing demonstrated the safety of the films in BALB/c mice, and the pharmacokinetic analysis demonstrated the delivery of lidocaine primarily to the vaginal tissue. We demonstrate the ability to develop a mucoadhesive, biodissolvable thin film and fine-tune drug release kinetics to optimize local delivery of lidocaine to the vulva.

Binder jetting 3D printing of challenging medicines: From low dose tablets to hydrophobic molecules

Increasing access to additive manufacturing technologies utilising easily available desktop devices opened novel ways for formulation of personalized medicines. It is, however, challenging to propose a flexible and robust formulation platform which can be used for fabrication of tailored solid dosage forms composed of APIs with different properties (e.g., hydrophobicity) without extensive optimization. This manuscript presents a strategy for formulation of fast dissolving tablets using binder jetting (BJ) technology. The approach is demonstrated using two model APIs: hydrophilic quinapril hydrochloride (QHCl, logP = 1.4) and hydrophobic clotrimazole (CLO, logP = 5.4). The proposed printing method uses inexpensive, well known, and easily available FDA approved pharmaceutical excipients. The obtained model tablets had uniform content of the drug, excellent mechanical properties, and highly porous structure resulting in short disintegration time and fast dissolution rate. The tablets could be scaled and obtained in predesigned shapes and sizes. The proposed method may find its application in the early stages of drug development where high flexibility of the formulation is required and the amount of available API is limited.

Amorphous Drug-Polymer Salt with High Stability under Tropical Conditions and Fast Dissolution: The Challenging Case of Lumefantrine-PAA.

Lumefantrine (LMF), a high-mobility and easy-to-crystallize WHO drug for treating malaria, can form an amorphous salt with poly(acrylic acid) (PAA) that is remarkably stable against crystallization at high humidity and temperature and has fast dissolution rate. The amorphous salt up to 75% drug loading was synthesized under a mild slurry condition easily implemented in basic facilities for global health. Salt formation was confirmed by IR spectroscopy and the much elevated glass transition temperature. At 50% drug loading, the amorphous salt resists crystallization for at least 18 months under the highly stressful condition of 40°C and 75% RH. In contrast, the dispersion containing neutral LMF in PVP fully crystallized in 4 d and the dispersion in HPMCAS, a weak polyelectrolyte of lower charge density than PAA, crystallized by 50% in 7 d. The amorphous salt at 50% drug loading showed much faster dissolution than crystalline LMF: In SGF, the area under the curve (AUC) was 30 times larger within the gastric emptying time (4h); in FaSSIF, the enhancement was even larger - by 200 times. Nanodroplets were detected during the dissolution in SGF, possibly accounting for the apparent enhancement of dissolution rate. The LMF-PAA example as a challenging case, along with the previously reported clofazimine-PAA, demonstrates the general utility of amorphous drug-polymer salts to achieve high stability under tropical conditions and enhanced dissolution and bioavailability.

A Method for Manufacturing Flexible Microfluidic Chip Based on Soluble Material

In this paper, a novel method for manufacturing flexible microfluidic chips without bonding process is proposed, which combines 3D printing technology and material dissolution technology. The manufacturing process of the microfluidic chip is as follows: a soluble HIPS mold with a preset shape is manufactured by 3D printing and placed in a molten PDMS solution for solidification. Soak in the limonene material to dissolve the mold and form a microchannel in the cured PDMS. Experimental studies have shown that the temperature and concentration of the limonene solution have an important effect on the dissolution rate. A 0.62 cm3 HIPS mold has the fastest dissolution rate at 100°C and 50% concentration. The proposed method provided a new idea for fabricating flexible microfluidic chip. Compared to bonding process, it has the characteristics of not relying on complicated processing conditions and low manufacturing cost.

Preparation and optimization of fast disintegrating tablets of isosorbide dinitrate using lyophilization method for oral drug delivery.

Background: Orally disintegrating tabletsrapidly disintegrate in saliva and then swallowed without the need for water. Materials & methods: The orally disintegrating tablets were prepared by freeze-drying of an aqueous dispersion of isosorbide dinitrate containing a matrix former (gelatin), a cryoprotectant (mannitol), a plasticizer (glycerin) and a dissolution enhancer (Tween/polyethylene glycol). Results: Results demonstrated that the selected formulation, Ft9, disintegrated within 1 min and showed faster dissolution rate compared with the commercial tablet. Conclusion: Having a fast disintegration time, the developed lyophilized tablet does notneed to be swallowed as a whole. So, it is a convenient solid oral dosage form for the patients who have difficulty with swallowing such as the pediatric and elderly ones.

All-polymeric transient neural probe for prolonged in-vivo electrophysiological recordings

Transient bioelectronics has grown fast, opening possibilities never thought before. In medicine, transient implantable devices are interesting because they could eliminate the risks related to surgical retrieval and reduce the chronic foreign body reaction. Despite recent progress in this area, the potential of transient bioelectronics is still limited by their short functional lifetime owed to the fast dissolution rate of degradable metals, which is typically a few days or weeks. Here we report that a switch from degradable metals to an entirely polymer-based approach allows for a slower degradation process and a longer lifetime of the transient probe, thus opening new possibilities for transient medical devices. As a proof-of-concept, we fabricated all-polymeric transient neural probes that can monitor brain activity in mice for a few months, rather than a few days or weeks. Also, we extensively evaluated the foreign body reaction around the implant during the probe degradation. This kind of devices might pave the way for several applications in neuroprosthetics.

Optimization of taste-masked dapoxetine oral thin films using factorial design: in vitro and in vivo evaluation

Dapoxetine HCl is used for the treatment of premature ejaculation. Dapoxetine is primarily metabolized in the liver and kidney and its metabolites are inactive; resulting in reduced bioavailability. Also, one of the commonly encountered issues in the oral dapoxetine formulae is its bitter taste. Thus, the objective of this study was to develop and to optimize novel dapoxetine taste-masked oral thin films (OTFs), to offer a faster dissolution rate, rapid release pattern, lower liver metabolism, and better patient compliance. To achieve our goal, the applicability of either pullulan or maltodextrin as strip forming polymers were investigated in the preparation of (OTFs), while glycerol was used as a plasticizer. Also, the physicochemical characteristics of dapoxetine in a resinate complex with AmberLiteTM -IRP69 as taste masking were evaluated. Furthermore, a 23 factorial design was used to study and to optimize the effect of the independent variables (strip forming polymer (X1), glycerol (X2) and AmberLiteTM (X3) amounts) on the disintegration time (Y1), degree of elongation (Y2), and degree of in vitro drug release in phosphate buffer pH 6.8 at 5 minutes (Q5min, Y3) as responses. P2 batch (OTF) (pullulan 96 mg, glycerol 12 mg, AmberLiteTM 32 mg, and dapoxetine 30 mg) was identified as an optimized formulation showing an in vitro disintegration time 9.33 s, 35.56% elongation, and 91.43% Q5min; excellent in vivo disintegration time; good overall taste acceptability and stable resinate complex.

Dissolution Enhancement of Eplerenone using Solvent Melt Method

Background: Eplerenone (EPL) is a BCS class II drug, thus, having poor water solubility. The poor water solubility of this drug leads to poor dissolution and ultimately shows poor bioavailability. To overcome this problem, the solid dispersion of EPL was prepared in this study. Methods: This was accomplished by using the solvent melt method as the solid dispersion technique. In this method, Pluronic F-68 and F-127 were used as the carrier and different formulations were prepared using varying ratios of a drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of drug solution and carrier was prepared at 70°C, using the digital magnetic stirrer. The resultant mixture was dried at 40°C in a hot air oven and optimized EPL-solid dispersion was undergone for their characterization using drug content, drug entrapment efficiency (%) and drug loading content (%), Scanning Electron Microscopy (SEM), Infra-Red spectroscopy, Differential Scanning Calorimetry (DSC), stability study and in-vitro dissolution studies. Results: The result indicated that there was no interaction between EPL and Pluronics (Pluronic F-68 &amp; F-127), and optimized formulation (P127-2) of EPL-solid dispersion had encapsulation efficiency &gt; 95%. Experimental work also showed that optimized formulation has 31.7% of drug loading content which was greater than other existing solid dispersion having less than 30% of drug loading content. Out of different batches, the optimized batch exhibits the faster dissolution rate in comparison to other batches. It released the almost total amount of drug (98.96%) in 30 minutes. The stored ESM-solid dispersion also exhibited remarkable stability and remains in a solid state, when it was exposed to 25°C/60% relative humidity and room temperature (38ºC) for two months. Such stability was confirmed by DSC method. The DSC thermogram of optimized formulation exhibited a melting endotherm at an onset temperature of 160°C, a peak temperature of 165°C and a heat of fusion of 25.68 J/gm. Similarly, the DSC thermogram of the physical mixture of bulk EPL/- pluronic F-127 also exhibited the onset of temperature at 165°C, and a peak temperature at 171°C. Thus, the result indicated that both samples showed almost similar DSC pattern and no sample altered its state after the treatment of temperature and humidity used in stability testing. SEM study was also performed in this research and the result indicated that the particle size of optimized formulation was varied, having irregular matrices due to the porous nature of the carrier. Conclusion: Based on different findings, it can be concluded that the solvent melt method could be a potential method for preparing the solid dispersion of EPL like BCS class-II Drugs and will be able to solve the dissolution and solubilization related problem of poorly soluble drugs.

Lung retention and particokinetics of silver and gold nanoparticles in rats following subacute inhalation co-exposure

BackgroundInhalation exposure to nanomaterials in workplaces can include a mixture of multiple nanoparticles. Such ambient nanoparticles can be of high dissolution or low dissolution in vivo and we wished to determine whether co-exposure to particles with different dissolution rates affects their biokinetics.Methods and ResultsRats were exposed to biosoluble silver nanoparticles (AgNPs, 10.86 nm) and to biopersistent gold nanoparticles (AuNPs, 10.82 nm) for 28 days (6-h/day, 5-days/week for 4 weeks) either with separate NP inhalation exposures or with combined co-exposure. The separate NPs mass concentrations estimated by the differential mobility analyzer system (DMAS) were determined to be 17.68 ± 1.69 μg/m3 for AuNP and 10.12 ± 0.71 μg/m3 for AgNP. In addition, mass concentrations analyzed by atomic absorption spectrometer (AAS) via filter sampling were for AuNP 19.34 ± 2.55 μg/m3 and AgNP 17.38 ± 1.88 μg/m3 for separate exposure and AuNP 8.20 ± 1.05 μg/m3 and AgNP 8.99 ± 1.77 μg/m3 for co-exposure. Lung retention and clearance were determined on day 1 (6-h) of exposure (E-1) and on post-exposure days 1, 7, and 28 (PEO-1, PEO-7, and PEO-28, respectively). While the AgNP and AuNP deposition rates were determined to be similar due to the similarity of NP size of both aerosols, the retention half-times and clearance rates differed due to the difference in dissolution rates. Thus, when comparing the lung burdens following separate exposures, the AgNP retention was 10 times less than the AuNP retention at 6-h (E-1), and 69, 89, and 121 times lower less than the AuNP retention at PEO-1, PEO-7, and PEO-28, respectively. In the case of AuNP+AgNP co-exposure, the retained AgNP lung burden was 14 times less than the retained AuNP lung burden at E-1, and 26, 43, and 55 times less than the retained AuNP lung burden at PEO-1, PEO-7, and PEO-28, respectively. The retention of AuNP was not affected by the presence of AgNP, but AgNP retention was influenced in the presence of AuNP starting at 24 h after the first day of post day of exposure. The clearance of AgNPs of the separate exposure showed 2 phases; fast (T1/2 3.1 days) and slow (T1/2 48.5 days), while the clearance of AuNPs only showed one phase (T1/2 .81.5 days). For the co-exposure of AuNPs+AgNPs, the clearance of AgNPs also showed 2 phases; fast (T1/2 2.2 days) and slow (T1/2 28.4 days), while the clearance of AuNPs consistently showed one phase (T1/2 54.2 days). The percentage of Ag lung burden in the fast and slow clearing lung compartment was different between separate and combined exposure. For the combined exposure, the slow and fast compartments were each 50% of the lung burden. For the single exposure, 1/3 of the lung burden was cleared by the fast rate and 2/3 of the lung burden by the slow rate.ConclusionsThe clearance of AgNPs follows a two- phase model of fast and slow dissolution rates while the clearance of AuNPs could be described by a one- phase model with a longer half-time. The co-exposure of AuNPs+AgNPs showed that the clearance of AgNPs was altered by the presence of AuNPs perhaps due to some interaction between AgNP and AuNP affecting dissolution and/or mechanical clearance of AgNP in vivo.

Rational formulation engineering of fraxinellone utilizing 6-O-α-D-maltosyl-β-cyclodextrin for enhanced oral bioavailability and hepatic fibrosis therapy

Although Fraxinellone (Frax) isolated from Dictamnus albus L. possessed excellent anti-hepatic fibrosis activity, oral administration of Frax suffered from the inefficient therapeutic outcome in vivo due to negligible oral absorption. At present, the oral formulation of Frax is rarely exploited. For rational formulation design, we evaluated preabsorption risks of Frax and found that Frax was rather stable while poorly dissolved in the gastrointestinal tract (78.88 μg/mL), which predominantly limited its oral absorption. Further solubility test revealed the outstanding capacity of cyclodextrin derivatives (CDs) to solubilize Frax (6.8–12.8 mg/mL). This led us to study the inclusion complexes of Frax with a series of CDs and holistically explore their drug delivery performance. Characterization techniques involving 1H-NMR, FT-IR, DSC, PXRD, and molecular docking confirmed the most stable binding interactions when Frax complexed with 6-O-α-D-maltosyl-β-cyclodextrin (G2-β-CD-Frax). Notably, G2-β-CD-Frax exhibited the highest solubilizing capacity, fast dissolution rate, and superior Caco-2 cell internalization with no obvious toxicity. Pharmacokinetic studies demonstrated markedly higher oral bioavailability of G2-β-CD-Frax (5.8-fold that of free drug) than other Frax-CDs. Further, long-term administration of G2-β-CD-Frax (5 mg/kg) efficiently inhibited CCl4-induced hepatic fibrosis in the mouse without inducing any toxicity. Our results will inspire the continued advancement of optimal oral Frax formulations for anti-fibrotic therapy.

In-vitro characterization and cytotoxicity study of flutamide loaded cyclodextrin nanosponges

Cyclodextrin based nanosponge (CDNS) as a novel delivery system with solubility improvement ability was chosen for flutamide (FLT) encapsulating. This antiandrogen drug is commonly used for prostate cancer, and has low bioavailability through oral usage. The scope of this study was to characterize the best formulation of CDNSs for FLT loading and investigate their cell cytotoxicity. Two types of CDNSs were synthesized, and in-vitro tests such as particle size, zeta potential, loading percent, DSC, FTIR, and release tests were analyzed. Cellular study of the plain and loaded form of carrier was also tested in the PC3 cell line. DLS and TEM confirmed the nano-sized and sponge like structure of CDNSs. FTIR and DSC analysis showed the encapsulation of FLT into CDNSs. CDNS 1:4 showed not only high encapsulation but also a fast dissolution rate of FLT in comparison with CDNS 1:2. CDNS 1:4 with efficient cellular uptake (93.41% after 3 h) had almost no toxicity against the PC3 cell line. Free FLT displayed about two folds more toxic than FLT-CDNSs after 24 and 48 h at 0.1 mg/mL concentrations. Finally, CDNS 1:4 can be introduced as a non-toxic delivery system for FLT with dissolution rate improvement characteristic.

Fast-Dissolving Solid Dispersions for the Controlled Release of Poorly Watersoluble Drugs.

Solid dispersions offer many advantages for oral drug delivery of poorly water-soluble drugs over other systems, including an increase in drug solubility and drug dissolution. An improvement in drug absorption and the higher bioavailability of active pharmaceutical ingredients in the gastrointestinal tract have been reported in various studies. In certain circumstances, a rapid pharmacological effect is required for patients. Fastdissolving solid dispersions provide an ideal formulation in such cases. This report will provide an overview of current studies on fast-dissolving solid dispersions, including not only solid dispersion powders with fast dissolution rates but also specific dose form for the controlled release of poorly water-soluble drugs. Specifically, the applications of fast-dissolving solid dispersions will be described in every specific case. Moreover, pharmaceutical approaches and the utilization of polymers will be summarized. The classification and analysis of fastdissolving solid dispersions could provide insight into strategies and potential applications in future drug delivery developments.

Influence of Polyvinyl Alcohol (PVA) on PVA-Poly-N-hydroxyethyl-aspartamide (PVA-PHEA) Microcrystalline Solid Dispersion Films

This study was conducted to formulate buccal films consisting of polyvinyl alcohol (PVA) and poly-N-hydroxyethyl-aspartamide (PHEA), to improve the dissolution of the drug through the oral mucosa. Ibuprofen sodium salt was used as a model drug, and the buccal film was expected to enhance its dissolution rate. Two different concentrations of PVA (5% w/v and 7.5% w/v) were used. Solvent casting was used to prepare films, where a solution consisting of drug and polymer was cast and allowed to dry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to investigate the properties of films. In vitro dissolution studies were also conducted to investigate drug release. SEM studies showed that films containing a higher concentration of PVA had larger particles in microrange. FTIR studies confirmed the presence of the drug in films and indicated that ibuprofen sodium did not react with polymers. DSC studies confirmed the crystalline form of ibuprofen sodium when incorporated within films. In vitro dissolution studies found that the dissolution percentage of ibuprofen sodium alone was increased when incorporated within the film from 59 to 74%. This study led to the development of solid microcrystalline dispersion as a buccal film with a faster dissolution rate than the drug alone overcoming problem of poor solubility.

Cannabidiol aqueous solubility enhancement: Comparison of three amorphous formulations strategies using different type of polymers

Poor aqueous solubility of terpenophenolic compound Cannabidiol (CBD) is a major issue in the widespread use of this promising therapeutic polyphenol. Moreover, choosing the appropriate strategy to overcome this challenge is time-consuming and based on trial-error processes. The amorphous form of CBD provided higher aqueous solubility as well as faster dissolution rate in comparison with crystalline CBD. Nevertheless, amorphous forms of CBD tend to recrystallize. The aim of this study was to use three different strategies based on the stabilization of the amorphous form. Cyclodextrins (CH3αCD, HPβCD and HPγCD.), mesoporous silicas (Silsol® and Syloid® AL-1FP) and water soluble polymers (Kollidon® VA64, Kollidon® 12PF and Soluplus®) were processed by using the following techniques: freeze-drying, spray-drying, subcritical carbon dioxide impregnation or hot-melt extrusion. All the obtained formulations provided complete amorphous CBD, although the drug loading depend highly of the excipients. CBD-cyclodextrin formulations, processed by freeze-drying or spray-drying, and CBD-mesoporous silica formulations, processed by subcritical CO2 or by atmospheric impregnation, provided significant increase of aqueous solubility. While the use of Kollidon® 12PF did not provided significant increased solubility within 90min, Kollidon® VA64 has been highlighted as the excipient that exhibits the highest increase of aqueous solubility of this study. Finally, all formulations, excepted CBD-ALFP formulations, showed adequate stability within at least two months.

Characterization and Evaluation of the Solubility and Oral Bioavailability of Rutin-Ethanolate Solvate.

Rutin has many biological activities, but poor solubility and absorption limit its oral application. This study aimed to investigate the characterization of metastable rutin-ethanolate and its solubility and oral bioavailability. In this research, a soluble rutin/CH3CH2OH solvate (Form Π) was prepared by solvent crystallization. High-performance liquid chromatography, gas chromatograph, and 1H-NMR showed that Form Π was formed by rutin and ethanol in a molar ratio of 1:1. The changes of Fourier transform infrared spectroscopy and 1H-NMR spectrum and the density functional theory (DFT) calculation predicted hydrogen bond formation between 4'-O of rutin and -OH of ethanol. The results of morphology, solid state CP/MAS 13C-NMR, X-ray diffraction, and differential scanning calorimetry (DSC) revealed that Form Π is a novel polymorph that differs from Form Ι (rutin trihydrate). Form Π can be stored for a long time under sealed and dry conditions at 40°C but would gradually transform into Form Ι under humid conditions. Although Form Π is a new metastable polymorph relative to Form Ι, Form Π has better solubility and faster dissolution rate. Moreover, the bioavailability of Form Π was 2.04 times higher than that of Form Ι. This outcome implied that Form Π would be a prospective raw material of oral preparation.

Development and evaluation of crystalline inclusion complex of finasteride using electrospraying as a novel approach

Solid form of drug plays the central role in optimizing its physicochemical properties, thus discovery of new solid forms always provides more options to achieve the desirable pharmaceutical profiles of drugs. Recently, certain drugs have been found to form crystalline inclusion complexes (ICs) with multiple types of linear polymers, representing a new sub-category of pharmaceutical solids. In this study, Finasteride (FNS) was used as the model host and poly (ethylene glycol) (PEG) as the guest, to form ICs of drug with the purpose of offering solubility advantage. Electrospraying as a novel approach was used for production of micro-particles of crystalline ICs of FNS, as it gave narrow particle size distribution and dry powder as end product. The obtained dry powder was characterized using powder X-ray diffraction, NMR spectroscopy and other characterization methods. The results revealed that FNS formed ICs with the biodegradable hydrophilic polymer (PEG), thus offering a FNS-PEG ICs as a potential new solid form. Compared with pure FNS crystals the FNS-PEG ICs crystals showed significantly higher solubility and faster dissolution rates; making it more suitable to achieve higher drug release profiles. Results demonstrated the possibility of using drug-polymer ICs microparticles as solid forms, providing a new approach to design formulations with enhanced drug release. In a nutshell developed formulation was found to be suitable for enhancing water solubility of poorly soluble actives.

Using Self-Nanoemulsifying System to Improve Oral Bioavailability of a Pediatric Antiepileptic Agent Stiripentol: Formulation and Pharmacokinetics Studies

This study aimed to develop a self-nanoemulsifying drug delivery system (SNEDDS) for poorly water-soluble drug stiripentol (STP) with enhanced oral bioavailability. Optimal excipients were selected by constructing pseudo-ternary phase diagrams using determined solubilities of STP, and then the proper composition of SNEDDS was investigated by employing a central composite design method. The optimized SNEDDS was composed of oil (ethyl oleate 39.61%), surfactant (Cremophor® RH 40 43.18%), co-surfactant (1,2-propanediol 17.21%), and STP of 50mg/mL. The hydrodynamic size, zeta potential, and polydispersity index (PDI) were found to be 45.52 ± 1.99nm, - 21.67 ± 0.24mV, and 0.076 ± 0.011, respectively. The optimized STP-SNEDDS showed good stability in accelerated and dilution stability studies. It was also helpful to suppress STP degradation in acidic solution. Compared with STP suspension, STP-SNEDDS presented much faster dissolution rate. STP-SNEDDS successfully resulted in superior levels of Cmax and AUC0 → 6 h (4048.38 ± 704.54μg/L and 7754.58 ± 1489.37hμg/L, respectively) to STP suspension (1894.09 ± 1077.64μg/L and 3556.93 ± 2470.01hμg/L, respectively). The relative oral bioavailability of STP was 218.01%. The brain biodistribution studies showed that STP-SNEDDS presented significantly higher STP concentrations in the brain at 0.5h and 1h than that of STP suspension after administration. These findings indicated that a SNEDDS-based oral formulation of STP would be helpful for increasing its therapeutic potential.

Particle design of itraconazole by supercritical anti-solvent technology: Processing-microstructure-solubility relationship

Particle design in recent years has attempted to overcome solubility limitations in drug development. In this work, the particle microstructures of itraconazole (ITZ) were designed by a supercritical anti-solvent (SAS) process, with or without hydroxypropyl methylcellulose (HPMC) as the dispersing material, where the processing-microstructure-solubility relationship was investigated. The results showed that ITZ particles with different shapes and crystal forms were obtained, which enhanced the ITZ solubility from 4.4 μg/mL to 108.5 μg/mL. For the optimal sample, ITZ crystal transformed into amorphous state, resulting in high solubility and fast dissolution rate. Moreover, hydrogen bond interaction was formed between HPMC and ITZ, which could hinder the recrystallization of dissolved ITZ, resulting in its complete dissolution. Also, the production efficiency was increased to 38.5 mg ITZ/min, which laid a foundation for the scale-up. These results show the great potential of SAS process on the particle design of poorly soluble drugs for solubility enhancement.

Leveraging Framework Instability: A Journey from Energy Storage to Drug Delivery

Amorphous pharmaceuticals often suffer from poor physical stability, which can negate their high solubility, fast dissolution rate, and better oral bioavailability vs. crystalline forms. This represents a major hurdle to processing, storage, and delivery of amorphous pharmaceuticals. Several approaches to addressing these problems have been pursued, but there is still a need for a general method for stabilizing the amorphous form. We describe a novel approach using a water-unstable metal-organic framework as a drug delivery vehicle that demonstrates improved amorphous form stability accompanied by remarkably enhanced solubility and a fast dissolution rate. This research project spanned eleven years from conception to realization and dissemination. With origins in understanding the stability or porous solids for energy storage materials, the work also highlights potential of basic science understanding to illuminate new areas of application.

Development and solidification of multifunction stabilizers formulated self-assembled core-shell Deacetyl mycoepoxydience nanosuspensions

In this study, a novel core-shell structure Deacetyl mycoepoxydience nanosuspensions (CS-DM-NSs) delivery system was successfully designed by self-assembly method and the solidification technology was also investigated. The Deacetyl mycoepoxydience (DM) nanocrystals core was prepared by anti-solvent precipitation with folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG2000-FA) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as functional stabilizers. Then the DM nanocrystals core was completely wrapped by the polyethylene glycol-hyaluronic acid (PEG-HA) as shell. To improve the stability, the CS-DM-NSs were solidified by spray-drying and freeze-drying, respectively. The influence of the solidification approach on the solidified powders was demonstrated by TEM and SEM. Compared with the freeze dried CS-DM-NSs, the spray dried powder presented spherical in shape with smooth surface. The dissolution velocity of the two powders was higher than to the raw drug (3.5-fold and 4.5-fold, respectively). The solidified CS-DM-NSs presented dose- and time- dependent cytotoxicity to cancer cells (MCF-7) and significantly higher cytotoxicity than the free DM. In addition, there was no significant difference between the spray-drying and the freeze-drying solidified CS-DM-NSs. Overall, the CS-DM-NSs showed promising potential as a drug carrier for cancer therapy and the spray drying could be confidently used for the CS-DM-NSs solidification with higher stability, smaller particle size, and faster dissolution rate.