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In this proof-of-concept study, we aimed to develop an anti-inflammatory patch that in contrast to the semi-solid standard therapy is dry and non-greasy, and only needs to be changed once a day due to continuous release of the active ingredient over 24 h. While fiber materials for the treatment of inflammatory skin diseases have been reported in the literature, the majority of studies focuses solely on material characterization including in vitro release studies; however, there is a lack of ex vivo permeation studies as well as comparison with standard therapy. However, such experiments are crucial to deduct the potential efficacy of the drug delivery system, as skin absorption of the drug may be the rate-limiting step and not the drug release. Therefore, we set out to investigate different types of electrospun fiber systems based on polycaprolactone, a polymer with a well-established safety profile widely used for fabricating electrospun patches. The electrospun fiber patches were loaded with the anti-inflammatory drug hydrocortisone and characterized not only for their drug release properties, but for the first time also for their skin permeation and retention as well as their cytocompatibility and anti-inflammatory properties on human skin. While in the release studies, the layer-by-layer fiber system proved to be best suited for an application time of 24 h, this was not reflected in the permeation studies, where all fiber systems showed a similar skin permeation and retention of the drug. In our study set-up, a comparison with standard cream formulations revealed that electrospun fibers offer an advantage in terms of the permeated amount of hydrocortisone. Overall, this study supports the importance of conducting comparisons with standard therapies and, additionally, confirms that electrospun fibers are a promising dosage form for the controlled release of anti-inflammatory drugs for the treatment of inflammatory skin diseases.
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The formation of a biomolecular corona on nanoparticles in blood is a well-known phenomenon influencing in vivo performance. Analogous phenomena in other biological fluids, such as the formation of a gastrointestinal (GI) corona, remain under-investigated. The ingestion of medicines leads to the generation of drug particles in the GI fluids. Consequently, an understanding of the behavior of drug particles in the gut requires determination of the adsorption of bile components onto these drug particles. This work aims to elucidate the factors affecting adsorption of bile salts onto ritonavir (RTV) particles. Crystalline RTV particles were incubated with non-micellar or micellar bile salts and bile salt depletion from solution was measured using HPLC and small angle X-ray scattering (SAXS). HPLC results show that bile salts adsorb onto RTV particles, with greater adsorption observed for more hydrophobic bile salts, following the order sodium glycodeoxycholate (SGDC)>sodium taurodeoxycholate (STDC)>sodium glycochenodeoxycholate SGCDC>sodium glycocholate (SGC)>sodium taurocholate (STC). Increasing the ionic strength of the solution led to increased adsorption of STDC, where buffer containing 300â¯mM NaCl resulted in greater adsorption than 150â¯mM NaCl. Additionally, micellar bile salts showed greater affinity for RTV particles than unimeric bile salts. In contrast, the extent of bile salt depletion was unaltered by addition of phospholipid to form mixed micelles. SAXS analysis of mixed micelles after incubation with RTV particles confirms depletion of bile salt from the supernatant, evidenced by reduced intensity of the micellar scattering feature. In conclusion, this study investigated factors influencing bile salt adsorption onto drug particles, highlighting the need to consider adsorption of bile components in forming the GI-corona.
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This method paper describes currently used experimental methods to predict the drug-in-polymer solubility of amorphous solid dispersions and offers a combined approach for applying the Melting-point-depression method, the Recrystallization method, and the Melting-and-mixing method. It aims to describe and expand on the theoretical basis as well as the analytical methodology of the recently published Melting-and-mixing method. This solubility method relies on determining the relationship between drug loads and the enthalpy of melting and mixing of a crystalline drug in the presence of an amorphous polymer. This relationship is used to determine the soluble drug load of an amorphous solid dispersion from the recorded enthalpy of melting and mixing of the crystalline drug portion in a drug-polymer sample at equilibrium solubility. Due to the complex analytical methodology of the Melting-and-mixing method, a software solution called the Glass Solution Companion app was developed. Using this new tool, it is possible to calculate the predicted drug-in-polymer solubility and Flory-Huggins interaction parameter from experimental samples, as well as to generate the resulting solubility-temperature curve. This software can be used for calculations for all three experimental methods, which would be useful for comparing the applicability of the methods on a given drug-polymer system. Since it is difficult to predict the suitability of these drug-in-polymer solubility methods for a specific drug-polymer system in silico, some experimental investigation is necessary. By optimizing the experimental protocol, it is possible to collect data for the three experimental methods simultaneously for a specific drug-polymer system. These results can then be readily analyzed using the Glass Solution Companion app to find the most appropriate method for the drug-polymer system, and therefore, the most reliable drug-in-polymer solubility prediction.
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Polímeros , Solubilidade , Polímeros/química , Preparações Farmacêuticas/química , Fluxo de Trabalho , Cristalização , Química Farmacêutica/métodos , Software , Temperatura de TransiçãoRESUMO
Terpene-based eutectic mixtures (EMs) are attractive platforms for transdermal delivery due to their solubilizing potential and ability to alter the barrier function of the stratum corneum (SC). Despite this, little is known about the effect of diluting EMs with co-solvents (CSs) on their solubility- and permeation-enhancing properties. Furthermore, insufficient attention has been paid to comparing these platforms with traditional solvents, such as propylene glycol (PG) or ethanol (EtOH). To address this gap, the present study investigates the impact of the CS content in EM:CS blends on the transdermal delivery of clotrimazole (CLOT). Two CSs, PG and EtOH, and two terpene-based EMs, menthol:thymol and thymol:ß-citronellol, were used. Each of the EMs was investigated at two different molar ratios between the terpenes, with one being their eutectic point, to explore its potential benefit for skin permeation. At each step, properties of the blends were compared with those of pure CSs. The EM:CS blends showed a better solubilizing potential for CLOT than EMs or CSs on their own. A higher content of CSs in the blends resulted in a higher skin permeation and retention of CLOT, and a lower degree of disarrangement of the SC structure. Furthermore, the blends of EMs at their EPs led to overall poorer permeation profiles, implying that the permeation rate is more affected by the properties of the individual terpenes than by the specific ratio at the eutectic point between them. In conclusion, addition of CSs to the EMs promotes permeation and retention of CLOT, while reducing the skin impairment caused by the terpenes.
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Administração Cutânea , Etanol , Mentol , Propilenoglicol , Absorção Cutânea , Pele , Solubilidade , Solventes , Terpenos , Absorção Cutânea/efeitos dos fármacos , Animais , Solventes/química , Terpenos/química , Terpenos/administração & dosagem , Pele/metabolismo , Etanol/química , Etanol/administração & dosagem , Mentol/química , Mentol/administração & dosagem , Propilenoglicol/química , Clotrimazol/administração & dosagem , Clotrimazol/química , Clotrimazol/farmacocinética , Permeabilidade , Timol/química , Timol/administração & dosagem , Suínos , Sistemas de Liberação de MedicamentosRESUMO
Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings - uniaxial, coaxial, and layer-by-layer - were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies - a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.
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Bandagens , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Piperidinas , Pirimidinas , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Piperidinas/química , Animais , Pirimidinas/administração & dosagem , Pirimidinas/farmacocinética , Suínos , Preparações de Ação Retardada/administração & dosagem , Pele/metabolismo , Pele/efeitos dos fármacos , Administração Cutânea , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Absorção Cutânea , Dermatopatias/tratamento farmacológico , Inflamação/tratamento farmacológico , Pirróis/administração & dosagem , Pirróis/química , Pirróis/farmacocinéticaRESUMO
The influence of different preparation methods on the physicochemical properties of amorphous solid forms have gained considerable attention, especially with recent publications on pharmaceutical polyamorphism. In the present study, we have investigated the possible occurrence of polyamorphism in the drug celecoxib (CEL) by investigating the thermal behavior, morphology, structure, molecular mobility and physical stability of amorphous CEL obtained by quench-cooling (QC), ball milling (BM) and spray drying (SD). Similar glass transition temperatures but different recrystallization behaviors were observed for CEL-QC, CEL-BM and CEL-SD using modulated differential scanning calorimetry analysis. A correlation between the different recrystallization behaviors of the three CEL amorphous forms and the respective distinct powder morphologies, was also found. Molecular dynamics simulations however, reveal that CEL presents similar molecular conformational distributions when subjected to QC and SD. Moreover, the obtained molecular conformational distributions of CEL are different from the ones found in its crystal structure and also from the ones found in the lowest-energy structure obtained by quantum mechanical calculations. The type and strength of CEL hydrogen bond interactions found in CEL-QC and CEL-SD systems are almost identical, though different from the ones presented in the crystal structure. Pair distribution function analyses and isothermal microcalorimetry show similar local structures and structural relaxation times, respectively, for CEL-QC, CEL-BM and CEL-SD. The present work shows that not only similar physicochemical properties (glass transition temperature, and structural relaxation time), but also similar molecular conformational distributions were observed for all prepared CEL amorphous systems. Hence, despite their different recrystallization behaviors, the three amorphous forms of CEL did not show any signs of polyamorphism.
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Varredura Diferencial de Calorimetria , Celecoxib , Cristalização , Simulação de Dinâmica Molecular , Temperatura de Transição , Celecoxib/química , Estabilidade de Medicamentos , Ligação de Hidrogênio , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Pós/químicaRESUMO
This study aimed to develop chitosan alginate nanoparticles (CANPs) for enhanced stability for dermal delivery of protein hydrolysate from Acheta domesticus (PH). CANPs, developed using ionotropic pre-gelation followed by the polyelectrolyte complex technique, were characterized for particle size, polydispersity index (PDI), and zeta potential. After the incorporation of PH into CANPs, a comprehensive assessment included encapsulation efficiency, loading capacity, morphology, chemical analyses, physical and chemical stability, irritation potential, release profile, skin permeation, and skin retention. The most optimal CANPs, comprising 0.6 mg/mL sodium alginate, 1.8 mg/mL calcium chloride, and 0.1 mg/mL chitosan, exhibited the smallest particle size (309 ± 0 nm), the narrowest PDI (0.39 ± 0.01), and pronounced negative zeta potential (-26.0 ± 0.9 mV), along with an encapsulation efficiency of 56 ± 2%, loading capacity of 2.4 ± 0.1%, release of 40 ± 2% after 48 h, and the highest skin retention of 12 ± 1%. The CANPs induced no irritation and effectively enhanced the stability of PH from 44 ± 5% of PH remaining in a solution to 74 ± 4% after three-month storage. Therefore, the findings revealed the considerable potential of CANPs in improving PH stability and skin delivery, with promising applications in cosmetics and related fields.
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It is generally accepted that water, as an effective plasticizer, decreases the glass transition temperatures (Tgs) of amorphous drugs, potentially resulting in physical instabilities. However, recent studies suggest that water can also increase the Tgs of the amorphous forms of the drugs prilocaine (PRL) and lidocaine (LID), thus acting as an anti-plasticizer. To further understand the nature of the anti-plasticizing effect of water, interactions with different solvents and the resulting structural features of PRL and LID were investigated by Fourier transform infrared spectroscopy (FTIR) and quantum chemical simulations. Heavy water (deuterium oxides) was chosen as a solvent, as the deuterium and hydrogen atoms are electronically identical. It was found that substituting hydrogen with deuterium showed a minimal impact on the anti-plasticization of water on PRL. Ethanol and ethylene glycol were chosen as solvents to compare the hydrogen bonding patterns occurring between the hydroxyl groups of the solvents and PRL and LID. Comparison of the various Tgs showed a weaker anti-plasticizing potential of these two solvents on PRL and LID. The frequency shifts of the amide CîO groups of PRL and LID due to the interactions with water, heavy water, ethanol, and ethylene glycol as observed in the FTIR spectra showed a correlation with the binding energies calculated by quantum chemical simulations. Overall, this study showed that the combination of weak hydrogen bonding and strong electrostatic contributions in hydrated PRL and LID could play an important role in inducing the anti-plasticizing effect of water on those drugs.
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Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.
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Polietilenoglicóis , Polietilenoglicóis/química , Solubilidade , Carvedilol/química , Estabilidade de Medicamentos , Polímeros/química , Lactonas/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodosRESUMO
Acheta domesticus is an edible insect, rich in nutritional value and considered a sustainable protein source. This study aimed to investigate the potential application of A. domesticus extracts for anti-skin-aging purposes. The extracts were prepared by maceration at ambient temperature with 95% ethanol or hexane and maceration in gentle heat (45 °C) with 95% v/v ethanol or DI water. The extracts were examined for total protein, phenolic, and flavonoid contents. Protein molecular weight distribution was analyzed. The safety of the extracts was investigated in terms of irritation and cytotoxicity. Biological activities relevant to the inhibition of skin aging were evaluated, including increasing transforming growth factor-beta 1 (TGF-ß1) expression and inhibitory activities on collagenase and hyaluronidase. The aqueous extract from maceration in gentle heat had the highest total protein content (63 ± 1% w/w), total phenolic content (0.48 ± 0.03 mg GAE/g extract), TGF-ß1 stimulating activities (33 ± 2 pg/mL), and collagenase inhibition (with a half maximal inhibitory concentration of 26 ± 1 µg/mL) among various extracts investigated. It caused no irritation to the hen's egg chorioallantoic membrane and showed no cytotoxicity to human dermal fibroblasts and peripheral blood mononuclear cells. Therefore, aqueous A. domesticus extract is proposed as an innovative natural anti-skin-aging ingredient.
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Design of inhalable mRNA therapeutics is promising because local administration in the respiratory tract is minimally invasive and induces a local response. However, several challenges related to administration via inhalation and respiratory tract barriers have so far prevented the progress of inhaled mRNA therapeutics. Here, we investigated factors of importance for lipid nanoparticle (LNP)-mediated delivery of mRNA to the respiratory tract. We hypothesized that: (i) the PEG-lipid content is important for providing colloidal stability during aerosolization and for mucosal delivery, (ii) the PEG-lipid contentinfluences the expression of mRNA-encoded protein in the lungs, and (iii) the route of administration (nasal versus pulmonary) affects mRNA delivery in the lungs. In this study, we aimed to optimize the PEG-lipid content for mucosal delivery and to investigatethe effect of administration route on the kinetics of protein expression. Our results show that increasing the PEG-lipid content improves the colloidal stability during the aerosolization process, but has a negative impact on the transfection efficiencyin vitro. The kinetics of protein expressionin vivois dependent on the route of administration, and we found that pulmonaryadministration of mRNA-LNPs to mice results inmore durable protein expression than nasaladministration. These results demonstrate that the design of the delivery system and the route of administration are importantfor achieving high mRNA transfection efficiency in the respiratory tract.
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Nanopartículas , Sistema Respiratório , Animais , Camundongos , Lipossomos , RNA Mensageiro , LipídeosRESUMO
It is generally accepted that water as a plasticizer can decrease the glass transition temperatures (Tgs) of amorphous drugs and drug excipient systems. However, previous studies suggest that water, as an anti-plasticizer, can increase the Tgs of co-amorphous systems of prilocaine (PRL) and lidocaine (LID). In order to investigate the intermolecular interactions between water and co-amorphous PRL-LID systems, Fourier transform infrared spectroscopy (FTIR) and principal component analysis (PCA) were conducted. Water was found to bind with the carbonyl groups of PRL and LID molecularly evenly in the hydrated co-amorphous PRL-LID systems. Quantum chemical simulations visually confirmed the interactions between water and co-amorphous PRL-LID systems. Furthermore, the physical stability of hydrated co-amorphous PRL-LID systems was improved due to the anti-plasticizing effect of water, compared with the anhydrous samples. The preference of water to interact with the carbonyl groups of PRL and LID as binding sites could be associated with the anti-plasticizing effect of water on the co-amorphous PRL-LID systems.
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Lidocaína , Prilocaína , Prilocaína/química , Temperatura de Transição , Temperatura , Água , Espectroscopia de Infravermelho com Transformada de Fourier , Estabilidade de Medicamentos , Varredura Diferencial de Calorimetria , SolubilidadeRESUMO
Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.
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Excipientes , Água , Porosidade , Solubilidade , Difração de Raios XRESUMO
Ball milling is used, not only to reduce the particle size of pharmaceutical powders, but also to induce changes in the physical properties of drugs. In this work we prepared three crystal forms of furosemide (forms â , â ¡, and â ¢) and studied their solid phase transformations during ball milling. Powder X-ray diffraction and modulated differential scanning calorimetry were used to characterize the samples after each milling time on their path to amorphization. Our results show that forms â and III directly converted into an amorphous phase, while form â ¡ first undergoes a polymorphic transition to form â , and then gradually loses its crystallinity, finally reaching full amorphousness. During ball milling of forms â and â ¡, the glass transition temperature (Tg) of the amorphous fraction of the milled material remains almost unchanged at 75 °C and 74 °C, respectively (whilst the amorphous content increases). In contrast, the Tg values of the amorphous fraction of milled form III increase with increasing milling times, from 63 °C to 71 °C, indicating an unexpected phenomenon of amorphous-to-amorphous transformation. The amorphous fraction of milled forms I and II samples presented a longer structural relaxation (i.e., lower molecular mobility) than the amorphous fraction of milled form III samples. Moreover, the structural relaxation time remained the same for the increasing amorphous fraction during milling of forms I and II. In contrast, the structural relaxation times were always shorter for the amorphous fraction of form III, but increased with increasing amorphous content during milling, confirming amorphous-to-amorphous transformation.
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Furosemida , Cristalização/métodos , Temperatura , Temperatura de Transição , Difração de Raios X , Varredura Diferencial de Calorimetria , Estabilidade de MedicamentosRESUMO
Functionalized calcium carbonate (FCC), a novel pharmaceutical excipient, has shown promising properties in the field of oral drug delivery. The current study aimed at evaluating the feasibility of FCC as a carrier for the solidification of self-nanoemulsifying drug delivery systems (SNEDDS) containing the poorly water-soluble model drug carvedilol (CRV). Conventional, subsaturated SNEDDS (80 %-SNEDDSliquid) and supersaturated SNEDDS (200 %-SNEDDSliquid) were loaded onto FCC via physical adsorption at three ratios; 2.5:1, 3.0:1 and 3.5:1 (w/w) of FCC:SNEDDSliquid, respectively, generating free-flowing powders (SNEDDSFCC) with drug loading ranging from 0.8 % to 2.6 % (w/w) CRV. The emulsification of SNEDDSFCC in a USP II dissolution setup (in purified water) was characterized using dynamic light scattering, resulting in similar droplet sizes and PDIs as observed for their liquid counterparts. The morphology and physical state of the obtained SNEDDSFCC were characterized using scanning electron microscopy and differential scanning calorimetry. The physical stability and drug release upon dispersion were assessed as a function of storage time. The 200 %-SNEDDSliquid were physically stable for 6 days, however, solidification using FCC stabilized the supersaturated concentrations of CRV for a test period of up to 10 weeks (solidification ratios 3.0:1 and 3.5:1 (FCC:SNEDDSliquid)). SNEDDSFCC achieved an improved rate and extent of drug release upon dispersion compared to the crystalline CRV in tap water (pH 7.5), however, to a lesser extent than their liquid counterparts. After 8 weeks of storage (25 °C at dry conditions), FCC was still able to rapidly release the SNEDDSliquid and demonstrated the same rate and extent of drug release as freshly prepared samples. The solidification of 200 %-SNEDDSliquid in presence of FCC greatly improved the drug loading and showed an enhanced drug release profile compared to the conventional systems. In conclusion, FCC showed potential as a carrier for solidification of SNEDDS and for the development of novel supersaturated solid SNEDDS for the oral delivery of poorly water-soluble drugs.
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Carbonato de Cálcio , Nanopartículas , Solubilidade , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Preparações Farmacêuticas , Água/química , Emulsões/química , Nanopartículas/química , Tamanho da Partícula , Administração Oral , Disponibilidade BiológicaRESUMO
Skin diseases are among the most common diseases in the global population and with the growth of the aging population, they represent an increasing burden to healthcare systems worldwide. Even though they are rarely life-threatening, the suffering for those affected is high due to the visibility and physical discomfort related to these diseases. Typical symptoms of skin diseases include an inflamed, swollen or itchy skin, and therefore, there is a high demand for effective therapy options. In recent years, electrospinning has attracted considerable interest in the field of drug delivery. The technique allows producing multifunctional drug-loaded fibrous patches from various natural and synthetic polymers with fiber diameters in the nano- and micrometer range, suitable for the treatment of a wide variety of skin diseases. The great potential of electrospun fiber patches not only lies in their tunable drug release properties and the possibility to entrap a variety of therapeutic compounds, but they also provide physical and mechanical protection to the impaired skin area, exhibit a high surface area, allow gas exchange, absorb exudate due to their porous structure and are cytocompatible and biodegradable. In the case of wound healing, cell adhesion is promoted due to the resemblance of the electrospun fibers to the structure of the native extracellular matrix. This review gives an overview of the potential applications of electrospun fibers in skin therapy. In addition to the treatment of bacterial, diabetic and burn wounds, focus is placed on inflammatory diseases such as atopic dermatitis and psoriasis, and therapeutic options for the treatment of skin cancer, acne vulgaris and herpes labialis are discussed. While we aim to emphasize the great potential of electrospun fiber patches for the treatment of skin diseases with this review paper, we also highlight challenges and limitations of current research in the field.
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Dermatopatias , Pele , Humanos , Idoso , Cicatrização , Dermatopatias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Polímeros/químicaRESUMO
Polyamorphism has been a controversial and highly debated solid-state phenomenon in both material and pharmaceutical communities. Although some evidence of this fascinating phenomenon has been reported for several inorganic systems, and more recently also for a few organic compounds, the occurrence of polyamorphism is poorly understood and the molecular-level organization of polyamorphic forms is still unknown. Here we have investigated the occurrence of polyamorphism and polyamorphic interconversions in hydrochlorothiazide (HCT), using both experimental and computational methods. Three distinct HCT polyamorphs, presenting distinct physical and thermal stabilities as well as distinct relaxation properties, were systematically prepared using spray-drying (SD), quench-cooling (QC) and ball milling (BM) methods. HCT polyamorph II (obtained by QC) was found to be more physically stable than polyamorphs I and III (obtained by SD and BM, respectively). Furthermore, polyamorphs I and III could be converted into polyamorph II after QC, while polyamorph II did not convert to any other polyamorph after SD or BM. Molecular dynamics simulations show that HCT dihedral angle distributions are significantly different for polyamorphs I and II, which is postulated as a possible explanation for their different physicochemical properties.
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The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.
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Nanopartículas , Distribuição Tecidual , Trato Gastrointestinal , Administração Oral , Preparações FarmacêuticasRESUMO
The solid state of matter is the preferred starting point for designing a pharmaceutical product. This is driven by both patient preferences and the relative ease of supplying a solid pharmaceutical product with desired quality and performance. Solid form diversity is increasingly prevalent as a crucial element in designing these products, which underpins the importance of solid-state analytical methods. This paper provides a critical analysis of challenges related to solid-state analytics, as well as considerations and suggestions for feasible and meaningful pharmaceutical analysis.