RESUMO
In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of a semi-solid extrusion method to create BFs from zein-Poly-Vinyl-Pyrrolidone (zein-PVP) polymer blend, which served as a carrier for drug (miconazole) and taste enhancers. After manufacturing, it was determined that the disintegration time for all films was less than 10 min. However, these films are designed to adhere to buccal tissue, ensuring sustained drug release. Approximately 80% of the miconazole was released gradually over 2 h from the zein/PVP matrix of the 3D printed films. Moreover, a detailed physicochemical characterization including spectroscopic and thermal methods was conducted to assess solid state and thermal stability of film constituents. Mucoadhesive properties and mechanical evaluation were also studied, while permeability studies revealed the extent to which film-loaded miconazole permeates through buccal tissue compared to commercially available oral gel formulation. Histological evaluation of the treated tissues was followed. Furthermore, in vitro antifungal activity was assessed for the developed films and the commercial oral gel. Finally, films underwent a two-month drug stability test to ascertain the suitability of the BFs for clinical application. The results demonstrate that 3D-printed films are a promising alternative for local administration of miconazole in the oral cavity.
Assuntos
Antifúngicos , Candidíase Bucal , Liberação Controlada de Fármacos , Miconazol , Impressão Tridimensional , Miconazol/administração & dosagem , Miconazol/química , Miconazol/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/química , Antifúngicos/farmacocinética , Administração Bucal , Candidíase Bucal/tratamento farmacológico , Humanos , Zeína/química , Mucosa Bucal/metabolismo , Mucosa Bucal/microbiologia , Povidona/química , Permeabilidade , Sistemas de Liberação de Medicamentos/métodos , Animais , Química Farmacêutica/métodos , CriançaRESUMO
Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer's and other neurodegenerative diseases. In the present work, a new high-performance liquid chromatography with fluorescence detection (HPLC-FLD) (λex. = 340 nm and λem. = 455 nm) method was developed and validated for the study of substance permeability in the central nervous system (CNS). Analysis was performed on a RP-C18 column with a binary gradient elution system consisting of methanol-potassium phosphate buffer solution (pH = 7.0, 0.02 M) as mobile phase. Samples of homotaurine and histidine (internal standard) were initially derivatized with ortho-phthalaldehyde (OPA) (0.01 M), N-acetylcysteine (0.01 M) and borate buffer (pH = 10.5; 0.05 M). To ensure the stability and efficiency of the reaction, the presence of different nucleophilic reagents, namely (a) 2-mercaptoethanol (2-ME), (b) N-acetylcysteine (NAC), (c) tiopronin (Thiola), (d) 3-mercaptopropionic acid (3-MPA) and (e) captopril, was investigated. The method was validated (R2 = 0.9999, intra-day repeatability %RSD < 3.22%, inter-day precision %RSD = 1.83%, limits of detection 5.75 ng/mL and limits of quantification 17.43 ng/mL, recovery of five different concentrations 99.75-101.58%) and successfully applied to investigate the in vitro permeability of homotaurine using Franz diffusion cells. The apparent permeability (Papp) of HOM was compared with that of memantine, which is considered a potential therapeutic drug for various CNSs. Our study demonstrates that homotaurine exhibits superior permeability through the simulated blood-brain barrier compared to memantine, offering promising insights for enhanced drug delivery strategies targeting neurological conditions.
Assuntos
Acetilcisteína , Memantina , Acetilcisteína/química , Cromatografia Líquida de Alta Pressão/métodos , o-Ftalaldeído/química , Indicadores e Reagentes , Tiopronina , Reprodutibilidade dos TestesRESUMO
This article takes a step forward in understanding the mechanisms involved during the preparation and performance of cross-linked high-drug-loading (HDL) amorphous solid dispersions (ASDs). Specifically, ASDs, having 90 wt % poorly water-soluble drug indomethacin (IND), were prepared via in situ thermal cross-linking of poly(acrylic acid) (PAA) and poly(vinyl alcohol) (PVA) and thoroughly evaluated in terms of physical stability and in vitro supersaturation. Results showed that HDL ASDs having excellent active pharmaceutical ingredient (API) amorphous stability and prolonged in vitro supersaturation were prepared by fine tuning the cross-linking procedure. Unraveling of the processes involved during ASD's formation shed light on the significant role of the cross-linking conditions (i.e., temperature and time), the physicochemical properties of the API, and the hydrolysis level of the cross-linker as key factors in modulating ASD's stability. In-depth analysis of the prepared systems revealed the (1) reduction of API's molecular motions within the cross-linked polymeric networks (through API's strong spatial confinement), (2) the structural changes in the prepared cross-linked matrices (induced by the high API drug loading), and (3) the tuning of the cross-linking density via utilization of low-hydrolyzed PVA as the major mechanisms responsible for ASD's exceptional performance. Complementary analysis by means of molecular dynamics simulations also highlighted the vital role of strong drug-polymer intermolecular interactions evolving among the ASD components. Overall, the impression of the complexity of in situ cross-linked ASDs has been reinforced with the excessive variation of parameters investigated in the current study, offering thus insights up to the submolecular level to lay the groundwork and foundations for the comprehensive assessment of a new emerging class of HDL amorphous API formulations.
Assuntos
Estabilidade de Medicamentos , Indometacina/química , Reagentes de Ligações Cruzadas , Composição de Medicamentos , Liberação Controlada de Fármacos , Simulação de Dinâmica MolecularRESUMO
Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.
Assuntos
Canabidiol/administração & dosagem , Canabinoides/administração & dosagem , Nanofibras/química , Administração Oral , Canabidiol/química , Canabinoides/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Ácidos Polimetacrílicos/química , Povidona/químicaRESUMO
Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API's (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the "cheerios effect" that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API's of the formulation and the resemblance of their PK behavior with previously reported data.
Assuntos
Anti-Hipertensivos , Diltiazem , Humanos , Idoso , Preparações de Ação Retardada/química , Comprimidos/química , Liberação Controlada de Fármacos , Hidroclorotiazida , Impressão Tridimensional , Tecnologia Farmacêutica/métodosRESUMO
Capsaicin (CAP) has been implicated as a gastroprotective agent in the treatment of peptic ulcers. However, its oral administration is hampered by its poor aqueous solubility and caustic effect at high administered doses. To address these limitations, we describe the development of gastric floating, sustained release electrospun films loaded with CAP. The nanofiber films were formulated using the polymers Eudragit RL/RS and sodium bicarbonate (SB) as the effervescent agent. The films were tested for their physicochemical properties, and film buoyancy and in vitro release of CAP were assessed in simulated gastric fluid. The cytocompatibility and anti-inflammatory properties of the films were evaluated in lipopolysaccharide (LPS)-stimulated Caco-2 cells. The amorphous films showed improved wettability, a short floating lag time (<1 s) and a total floating time of over 24 h accompanied by sustained CAP release for up to 24 h. CAP-loaded films demonstrated biocompatibility with Caco-2 cells and potential cytoprotective effects by attenuating inflammatory cytokine and reactive oxygen species (ROS) production in LPS-stimulated Caco-2 cells. The gastric floating electrospun films could serve as a platform for sustained and stomach-specific drug delivery applications.
Assuntos
Capsaicina , Lipopolissacarídeos , Humanos , Preparações de Ação Retardada/química , Células CACO-2 , Sistemas de Liberação de Medicamentos , Solubilidade , ComprimidosRESUMO
INTRODUCTION: Medication errors during drug manipulations in pediatric care pose significant challenges to patient safety and optimal medication management. Epidemiological studies have revealed a high prevalenceof medication errors throughout the medication process. Due to the lack of age-appropriate dosage forms, medication manipulation is common in pediatric drug administration. The consequences of these manipulations on drug efficacy and safety could be devastating, highlighting the need for evidence-based guidelines and standardized compounding practices. AREAS COVERED: This review focuses on examining medication errors in pediatric care and delving into the manipulation of medicinal products. EXPERT OPINION: The observed prevalence of medication errors and manipulations underscores the importance of addressing these issues to enhance patient safety and improve medication outcomes in pediatric care. Overall, the development of age-appropriate formulations and the dissemination of comprehensive clinical guidelines are essential steps toward improving medication safety and minimizing manipulations in pediatric healthcare settings.
Assuntos
Erros de Medicação , Segurança do Paciente , Humanos , Criança , Erros de Medicação/prevenção & controle , Preparações Farmacêuticas , Composição de MedicamentosRESUMO
Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.
Assuntos
Deglutição , Omeprazol , Animais , Suínos , Sistemas de Liberação de Medicamentos , Administração Oral , Alginatos , Administração Bucal , Mucosa BucalRESUMO
Pharmaceutical compounding is a core activity in the preparation of patient-specific dosage forms. In the current study we aimed to investigate whether 3D printing could be employed for the preparation of pediatric-friendly personalized dosage forms that fulfil the acceptance criteria specified in the pharmacopoeias for conventional dosage forms. We then compared the 3D printed dosage forms with the same formulations prepared with mold-casting, a method frequently applied during pharmaceutical compounding. The molded dosage forms failed to pass most of the quality control tests, including the mass uniformity and content uniformity tests, as well as dose accuracy, contrary to the 3D printed, which not only passed all tests but also enabled precision overdose adjustment. Hence, 3D printing of chocolate-based dosage forms may effectively serve as an acceptable alternative method to mold casting in compounding patient-specific medication at the point-of-care.
Assuntos
Chocolate , Composição de Medicamentos/métodos , Impressão Tridimensional , Tecnologia Farmacêutica/métodos , Criança , Formas de Dosagem , Composição de Medicamentos/normas , Humanos , Preparações Farmacêuticas , Controle de Qualidade , Tecnologia Farmacêutica/tendênciasRESUMO
Periodontal disease is associated with chronic inflammation and destruction of the soft and hard tissues in the periodontium. Scaffolds that would enable cell attachment and proliferation while at the same time providing a local sustained anti-inflammatory action would be beneficial in restoring or reversing disease progression. In the current study, silk sericin, a natural protein derived from the silkworm cocoons, was electrospun with poly lactide-co-glycolic acid (PLGA) and ketoprofen, and the composite scaffolds were assessed for their physicochemical and mechanical properties, as well as their biocompatibility and in vitro anti-inflammatory action. The composite scaffolds showed an increase in their hydrophilicity and an exceptional reinforcement of their mechanical properties, compared to plain PLGA scaffolds, sustaining drug release for up to 15 days. Human gingival fibroblasts showed a favorable attachment and proliferation on the composite scaffolds as visualized with scanning electron and confocal microscopy. A significant downregulation of the pro-inflammatory markers MMP-9 and MMP-3 and an upregulation of the anti-inflammatory gene IL-10 was achieved for lipopolysaccharide-stimulated RAW 264.7 macrophages after cultivation on the composite scaffolds. The current study demonstrated that silk sericin-PLGA composite scaffolds have the potential to simultaneously accommodate cell attachment and proliferation and achieve a sustained anti-inflammatory action in the treatment of periodontal diseases.
Assuntos
Sericinas , Engenharia Tecidual , Animais , Anti-Inflamatórios/farmacologia , Glicolatos , Humanos , Ácido Láctico/química , Camundongos , Periodonto , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Células RAW 264.7 , Sericinas/farmacologia , Alicerces Teciduais/químicaRESUMO
Treatment failure of endodontic infections and their concurrent inflammations is commonly associated with microbial persistence and reinfection, also stemming from the anatomical restrictions of the root canal system. Aiming to address the shortcomings of current treatment options, a fast-disintegrating nanofibrous film was developed for the intracanal coadministration of an antimicrobial (ZnO nanoparticles) and an anti-inflammatory (ketoprofen) agent. The electrospun films were fabricated based on polymers that dissolve rapidly to constitute the actives readily available at the site of action, aiming to eliminate both microbial infection and inflammation. The anti-inflammatory potency of the nanofiber films was assessed in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells after confirming their biocompatibility in the same cell line. The nanofiber films were found effective against Enterococcus faecalis, one of the most prominent pathogens inside the root canal space, both in vitro and ex vivo using a human tooth model experimentally infected with E. faecalis. The physical properties and antibacterial and anti-inflammatory potency of the proposed electrospun nanofiber films constitute a promising therapeutic module in the endodontic therapy of nonvital infected teeth. All manuscripts must be accompanied by an abstract. The abstract should briefly state the problem or purpose of the research, indicate the theoretical or experimental plan used, summarize the principal findings, and point out major conclusions.
Assuntos
Anti-Infecciosos , Infecções Bacterianas , Nanofibras , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Enterococcus faecalis , Humanos , Inflamação/tratamento farmacológico , Nanofibras/uso terapêuticoRESUMO
Child-appropriate dosage forms are critical in promoting adherence and effective pharmacotherapy in pediatric patients, especially those undergoing long-term treatment in low-resource settings. The present study aimed to develop orodispersible films (ODFs) for isoniazid administration to children exposed to tuberculosis. The ODFs were produced from the aqueous solutions of natural and semi-synthetic polymer blends using electrospinning. The spinning solutions and the resulting fibers were physicochemically characterized, and the disintegration time and isoniazid release from the ODFs were assessed in simulated salivary fluid. The ODFs comprised of nanofibers with adequate thermal stability and possible drug amorphization. Film disintegration occurred instantly upon contact with simulated salivary fluid within less than 15 s, and isoniazid release from the ODFs in the same medium followed after the disintegration profiles, achieving rapid and total drug release within less than 60 s. The ease of administration and favorable drug loading and release properties of the ODFs may provide a dosage form able to facilitate proper adherence to treatment within the pediatric patient population.