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1.
Tochukwu C. Okwuosa Dominika Stefaniak Basel Arafat Abdullah Isreb Ka-Wai Wan Mohamed A. Alhnan 《Pharmaceutical research》2016,33(11):2704-2712
Purpose
The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing.Methods
Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus.Results
Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern.Conclusions
Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.2.
Tochukwu C. Okwuosa Beatriz C. Pereira Basel Arafat Milena Cieszynska Abdullah Isreb Mohamed A. Alhnan 《Pharmaceutical research》2017,34(2):427-437
Purpose
Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing.Methods
The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC.Results
A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers.Conclusions
Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient’s needs.3.
Purpose
Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print “candy – like” formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability.Methods
Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug – excipient interactions and the content uniformity.Results
Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min.Conclusions
3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.4.
Purpose
The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations.Methods
The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions.Results
Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization.Conclusions
Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization.5.
Rania Hamed Ali Al-Samydai Tamadur Al Baraghthi Ola Tarawneh Suhair Sunoqrot 《Journal of pharmaceutical innovation》2017,12(1):62-75
Purpose
The objectives of this study were to develop once-a-day oral controlled-release tablets of quetiapine fumarate (QF) and to determine the effect of polymer type, viscosity grade, polymer ratio, and polymer rheological properties on the rate of QF release from hydroxypropyl methylcellulose (HPMC) matrix tablets.Methods
Tablets were prepared from low-viscosity-grade HPMC K100LV (K100LV), high-viscosity-grade HPMC K4M (K4M), Compritol® HD5 ATO (PEGylated glyceryl behenate (PGB)), and binary combinations of these polymers. In vitro drug release from all tablets was evaluated over 24 h.Results
In vitro drug release studies revealed that formulations containing K100LV/K4M and PGB/K4M at a ratio of 170:70 resulted in similar release profiles which extended for 24 h (f2 > 50). QF release kinetics followed either diffusion, anomalous transport, case II transport, or super case II transport, as fitted by the Korsmeyer-Peppas model. Tablet swelling and erosion studies were consistent with dissolution profiles. A linear relationship between % swelling and % QF released was observed in tablets containing K4M alone or in combination with K100LV or PGB, indicating the direct role of polymer swelling in controlling the mechanism of drug release. The viscoelastic properties of single and binary polymeric gels made with the three polymers (K100LV, K4M, and PGB) corroborated the in vitro release studies of QF tablets.Conclusions
Our results provide evidence that blending polymers with different viscosities and hydrophilicities can result in unique matrices with tunable release profiles.6.
Kateřina Punčochová Andrew V. Ewing Michaela Gajdošová Tomáš Pekárek Josef Beránek Sergei G. Kazarian František Štěpánek 《Pharmaceutical research》2017,34(5):990-1001
Purpose
Imaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution.Methods
Magnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier.Results
The crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner.Conclusions
Aprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process.7.
Michael Hodgman Michael G. Holland Ulrich Englich Susan M. Wojcik William D. Grant Erich Leitner 《Journal of medical toxicology》2016,12(4):391-395
Introduction
Whole bowel irrigation (WBI) is a management option for overdose of medications poorly adsorbed to activated charcoal, with modified release properties, or for body packers. Polyethylene glycol (PEG) is a mixture of ethylene oxide polymers of varying molecular weight. PEG with an average molecular weight of 3350 g/mol is used for WBI. PEG electrolyte lavage solution has been shown in vitro to hasten the dissolution of acetaminophen. The impact of PEG on the pharmacokinetics of extended release pharmaceuticals is unknown. Lower average molecular weight PEG mixtures are used as solvents and excipients. We sought to investigate the impact of PEG on the release of morphine from several extended release morphine formulations.Methods
An in vitro gastric model was developed. To test the validity of our model, we first investigated the previously described interaction of ethanol and Avinza®. Once demonstrated, we then investigated the effect of PEG with several extended release morphine formulations.Results
In the validation portion of our study, we confirmed an ethanol Avinza® interaction. Subsequently, we did not observe accelerated release of morphine from Avinza® or generic extended release morphine in the presence of PEG.Conclusion
The use of PEG for gastric decontamination following ingestion of these extended release morphine formulations is unlikely to accelerate morphine release and aggravate intoxication.8.
Bashar A. Alkhalidi Esra’a Albarahmieh Sami M.A. Qassim Manar A.L. Al-Asa’ad Hatim S. Alkhatib 《Journal of pharmaceutical innovation》2017,12(4):367-373
Purpose
The aim of the present work was to develop gastroretentive drug delivery system of gabapentin from different matrices prepared by hot melt or conventional wet granulation, which may enhance drug bioavailability. The influence of core type, granulation process, and coating level on the drug release rates was investigated.Methods
Tablet cores were prepared from hydrophilic system of hypermellose, carboxy melthyl celloulse, and Avicel or hydrophobic system of ethyl cellulose, alginic acid, and stearic acid. The tablets were coated by Eudragit RL with triethyl citrate and compressed directly. These tablets were evaluated according to their in vitro dissolution profiles and release mechanisms.Results
Hydrophobic matrices allowed the control of drug release. Hot melt granulation was an effective tool over wet granulation or coating for slowing release rates from hydrophobic tablets. Both hydrophobic polymer ratio and coating level influenced the drug release mechanism. The drug release of samples with minor proportion of ethyl cellulose and stearic acid or low Eudragit RL level was driven by anomalous transport and the increase of their proportions contributed to the erosion of the matrix.Conclusions
Hydrophobic core tablet prepared from hot melt granulation and coated by Eudragit RL has shown to be a promising formulation intended to gastroretentive gabapentin delivery system.9.
Zhiqiang Tian Qin Yu Yunchang Xie Fengqian Li Yi Lu Xiaochun Dong Weili Zhao Jianping Qi Wei Wu 《Pharmaceutical research》2016,33(8):1988-1997
Purpose
To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles.Methods
NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references.Results
NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation.Conclusion
Controlled release of integral NLCs is achieved by the osmotic pump strategy.10.
Purpose
In this study HPMC-eudragit based hydrodynamically balanced capsules of two model drugs; propranolol HCl and ofloxacin were prepared with the aim to have the gastric retention of the systems for longer periods of time with desired sustained/ controlled drug release.Methods
Gastro-retentive capsules were prepared by simple physical blending of various low density polymers and filling into capsules. These capsules were subjected to in vitro buoyancy/ matrix integrity and dissolution studies. Weight variation, content uniformity test, UV spectral analysis and placebo interaction studies were also performed.Results
Preliminary studies revealed that high soluble drug required higher polymer ratios to sustain drug release and maintain matrix integrity/ buoyancy than low soluble drug. In both the cases, with increase in HPMC and eudragit S100 levels there was an increase in matrix integrity and decrease in drug release rate, however much higher levels of eudragit S100 decreased matrix integrity and buoyancy. Lactose (release rate modifier) decreased matrix integrity, buoyancy and increased drug release. Mechanism of release in the both cases was found to be anomalous "non-fickian".Conclusion
From this research and the literature available on the eudragit and HPMC matrix systems, it is evident that different categories of drugs (suitable for gastric retention), ranging from freely soluble to sparingly soluble can be suitably formulated as HPMCeudragit based GR HBS capsules with desired drug release characteristics, provided no chemical instability/ incompatibility occurs between the drug and the polymers.11.
Hassana Hsein Ghislain Garrait Fahima Tamani Eric Beyssac Valérie Hoffart 《Pharmaceutical research》2017,34(2):365-377
Purpose
In earlier study, we proposed denatured whey protein (DWP) powder obtained by atomization as a new excipient to promote oral drug delivery. In this work, we evaluate the possibility to formulate tablets based on DWP powders and to characterize their role as a matrix mucoadhesive excipient.Methods
Tablets containing increased amount of DWP (10 to 30%) were produced by direct compression after mixing with theophylline, microcrystalline cellulose, Aerosil® and magnesium stearate. Dissolution behaviors of obtained tablets were evaluated in different USP buffers (pH 1.2, 4.5 and 6.8) and in simulated gastric and intestinal fluids and mechanisms analyzed by multiple mathematical models. Swelling, erosion and mucoadhesion were also evaluated. Finally, release and absorption were studied in the artificial digestive system (TIM 1).Results
Tablets based on DWP and containing 300 mg of theophylline were obtained by direct compression. These tablets exhibited controlled release driven by diffusion starting from 15% DWP content whatever the pH studied. They also showed a great extent of swelling and water uptake while matrix weight loss was limited. Addition of enzymes accelerated drug release which became governed by erosion according to Peppas model.Conclusions
The present study shows that DWP powders can be successfully used as a pharmaceutical excipient, and in particular as a matrix mucoadhesive controlled release tablets.12.
Ana Claudia Temer Maíra Teles Teixeira Livia Lira Sa-Barreto Tais Gratieri Guilherme Martins Gelfuso Izabel Cristina Silva Stephânia Fleury Taveira Ricardo N. Marreto Marcilio Cunha-Filho 《Journal of pharmaceutical innovation》2018,13(3):261-269
Purpose
Clinical practice suggests orally disintegrating tablets (ODTs) may be subdivided for dose adjustments, however there are no studies evaluating the effect of this practice in ODTs quality parameters. This work was therefore dedicated to elucidating the impact of the tablet subdivision on ten selected ODTs produced by different technologies.Methods
Structural properties were assessed using weight; dimensions; image analysis; moisture content and porosimetry evaluations. Functional evaluations were also performed by disintegration and wetting assays. Tablets were evaluated just after subdivision and after an accelerated aging.Results
Outcomes suggest the manufacturing method plays an important role in the suitability of ODTs for subdivision. While tablets containing granules immersed in a powdered matrix structure showed poor subdivision performance, with high weight variation and weight loss, tablets obtained by freeze-drying or direct compression of powder mixtures showed acceptable levels of these parameters and could be subdivided for immediate use. Aged tablets revealed structural and/or functional damages for all analyzed drug products, which includes softening of their matrices, water uptake and darkening, with loss of their disintegration and wetting capacities, which suggest inadequacy of ODTs subdivision for later use.Conclusions
The results exposed in this study could be useful for the clinical decision on the subdivision of this tablets category.13.
Jakub Sirc Zuzana Hampejsova Jana Trnovska Petr Kozlik Jakub Hrib Radka Hobzova Alena Zajicova Vladimir Holan Zuzana Bosakova 《Pharmaceutical research》2017,34(7):1391-1401
Purpose
The present study aims to prepare poly(D,L-lactic acid) (PLA) nanofibers loaded by the immunosuppressant cyclosporine A (CsA, 10 wt%). Amphiphilic poly(ethylene glycol)s (PEG) additives were used to modify the hydrophobic drug release kinetics.Methods
Four types of CsA-loaded PLA nanofibrous carriers varying in the presence and molecular weight (MW) of PEG (6, 20 and 35 kDa) were prepared by needleless electrospinning. The samples were extracted for 144 h in phosphate buffer saline or tissue culture medium. A newly developed and validated LC-MS/MS method was utilized to quantify the amount of released CsA from the carriers. In vitro cell experiments were used to evaluate biological activity.Results
Nanofibers containing 15 wt% of PEG showed improved drug release characteristics; significantly higher release rates were achieved in initial part of experiment (24 h). The highest released doses of CsA were obtained from the nanofibers with PEG of the lowest MW (6 kDa). In vitro experiments on ConA-stimulated spleen cells revealed the biological activity of the released CsA for the whole study period of 144 h and nanofibers containing PEG with the lowest MW exhibited the highest impact (inhibition).Conclusions
The addition of PEG of a particular MW enables to control CsA release from PLA nanofibrous carriers. The biological activity of CsA-loaded PLA nanofibers with PEG persists even after 144 h of previous extraction. Prepared materials are promising for local immunosuppression in various medical applications.14.
Purpose
To improve the pharmaceutical properties of amorphous ciprofloxacin (CIP) succinate salts via formulation as polymer/amorphous salt solid dispersions (ASSDs).Methods
ASSDs consisting of an amorphous CIP/succinic acid 1:1 or 2:1 salt dispersed in PVP or Soluplus were produced by spray drying and ball milling. The solid state characteristics, miscibility, stability, solubility and passive transmembrane permeability of the ASSDs were then examined.Results
The ASSDs had higher glass transition and crystallization temperatures than the corresponding amorphous succinate salts, and were also more stable during long-term stability studies. The results of inverse gas chromatography and thermal analysis indicated that the salts and polymers form a miscible mixture. The solubility of the pure drug in water and biorelevant media was significantly increased by all of the formulations. The permeability of the ASSDs did not differ significantly from that of the amorphous CIP succinate salts, however all samples were less permeable than the pure crystalline drug.Conclusions
The formulation of amorphous CIP succinate salts as ASSDs with polymer improved their long-term stability, but did not significantly affect their solubility or permeability.15.
Haibo Qu Marius C. Costache Saadet Inan Alan Cowan David Devore Paul Ducheyne 《Pharmaceutical research》2016,33(3):729-738
Purpose
Polymer-xerogel composite materials have been introduced to better optimize local anesthetics release kinetics for the pain management. In a previous study, it was shown that by adjusting various compositional and nano-structural properties of both inorganic xerogels and polymers, zero-order release kinetics over 7 days can be achieved in vitro. In this study, in vitro release properties are confirmed in vivo using a model that tests for actual functionality of the released local anesthetics.Methods
Composite materials made with tyrosine-polyethylene glycol(PEG)-derived poly(ether carbonate) copolymers and silica-based sol–gel (xerogel) were synthesized. The in vivo release from the composite controlled release materials was demonstrated by local anesthetics delivery in a rat incisional pain model.Results
The tactile allodynia resulting from incision was significantly attenuated in rats receiving drug-containing composites compared with the control and sham groups for the duration during which natural healing had not yet taken place. The concentration of drug (bupivacaine) in blood is dose dependent and maintained stable up to 120 h post-surgery, the longest time point measured.Conclusions
These in vivo studies show that polymer-xerogel composite materials with controlled release properties represent a promising class of controlled release materials for pain management.16.
Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions
Zhen Chen Kuan Yang Chengbin Huang Alan Zhu Lian Yu Feng Qian 《Pharmaceutical research》2018,35(2):38
Purpose
To study the effects of physicochemical properties of drug and polymer, as well as the drug-polymer interactions, on the surface composition of SDDs.Methods
Ethanol solutions containing a model drug (IMC, NMP or FCZ) and a model polymer (PVPK12, PVPK30 or PVP-VA) were spray dried, and the surface composition of SDDs was analyzed by XPS. The surface tensions of pure components and their solutions were measured using Wilhelmy plate and/or calculated using ACD/Labs. NMR and DLS were used to obtain the diffusion coefficients of IMC, NMP, PVPK12 and PVPK30 in solvents. Flory-Huggins interaction parameters for selected drug-polymer pairs were obtained using a melting point depression method.Results
Significant surface enrichment or depletion of the drug was observed in SDDs depending on the particular drug-polymer combination. With PVP as the dispersion polymer, IMC and NMP were surface enriched; whereas FCZ, a hydrophilic drug, was surface depleted. With increasing PVP molecular weight, the surface drug concentration increased, and the effect was greater in the NMP/PVP and FCZ/PVP systems than in the IMC/PVP system where strong drug-polymer interaction existed. Changing the polymer from PVP to PVP-VA reduced the surface concentration of the drug.Conclusions
The surface concentration of a SDD can be significantly different from the bulk concentration. The main results of this work are consistent with the notion that the relative surface tensions control surface enrichment or depletion. Besides, the relative diffusion rates of the components and the strength of their interactions may also affect the surface composition of the SDDs.17.
Saeed Shojaee Ali Nokhodchi Mohammed Maniruzzaman 《Journal of pharmaceutical innovation》2017,12(3):260-270
Purpose
This study examines the effect of sodium metabisulphite (SMB) as an antioxidant on the stability and release of various model drugs, namely, propranolol HCl, theophylline and zonisamide from the polyethylene oxide (PEO) tablets. The antioxidant was used to minimise degradation and instability of the manufactured tablets when stored at 40 °C (55 ± 5% RH) over 8 weeks.Method
Multiple batches of tablets weighing 240 mg (50% w/w) with a ratio of 1:1 drug/polymer and 1% (w/w) sodium metabisulphite containing different model drugs and various molecular weights of PEO 750 and 303 were produced.Results
The results indicated that the use of sodium metabisulphite marginally assisted in reducing drug release and degradation via oxidation in propranolol HCl tablets containing both PEO 750 and 303. In the case of poorly and semi-soluble drugs (zonisamide and theophylline), the formulations with both PEO showed entirely superimposable phenomenon and different release profiles compared to control samples (matrices without SMB). DSC study demonstrated the modifications of the polymer due to degradation and observed the effect of SMB on the thermal degradation of the PEO matrices.Conclusion
The use of antioxidant has assisted in retaining the stability of the manufactured tablets with different model drugs especially those with the highly soluble drug that are susceptible to rapid degradation. This has been reflected by an extended release profile of various drugs used at various stages of the storage time up to 8 weeks.18.
Pei T. Mah Dunja Novakovic Jukka Saarinen Stijn Van Landeghem Leena Peltonen Timo Laaksonen Antti Isomäki Clare J. Strachan 《Pharmaceutical research》2017,34(5):957-970
Purpose
To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods.Method
Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy.Results
Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage.Conclusions
SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.19.
Purpose
To compare traditional dialysis- and novel solvatofluorochromism (SFC)-based methods for accurate determination of drug release profiles for nanoparticle drug carriers.Methods
Polymer nanoassemblies (PNAs) varying in drug release patterns were prepared using poly(ethylene glycol), poly(ethylenimine), hydrophobic excipients (palmitate and deoxycholate), and model hydrophobic anticancer drugs with clinical relevance (carfilzomib and docetaxel). Nile blue (NB) was used as a model SFC dye quenching fluorescence in water yet emitting strong fluorescence in the presence of hydrophobic drugs within PNAs. Drug release kinetics were measured by dialysis- and SFC-based methods, and analyzed by mathematical modeling of free drug, spiked drug, and encapsulated drug release.Results
The dialysis method overestimated drug remaining in PNAs because it included released drug in measurements, whereas the SFC method successfully distinguished drugs entrapped in PNAs from released in solution and thus provided more accurate drug release patterns. However, mathematical modeling revealed that the dialysis method would be less influenced than the SFC method by hydrophobic excipients modulating drug diffusion within PNAs.Conclusions
In comparison to the dialysis-based method, the SFC-based method would allow for real-time spectroscopic determination of drug release from PNAs and potentially other nanoparticle drug carriers with improved convenience and accuracy.20.