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1.
Int J Pharm Compd ; 25(2): 100-103, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798108

RESUMEN

Healthy human skin performs a constellation of functions essential to good health, and the consequences of disruption to that effective external defense system have been recognized since antiquity. The earliest treatments for dermal injuries and diseases were compounded: They were prepared for each patient and could be modified to address progressive phases of healing. The benefits of that therapeutic approach continue today, made immeasurably more effective by modern pharmaceutical compounding. In this article, which is the first of several in a series that presents healing-drug profiles, various agents that can be compounded to enable dermal healing are described. Those drugs are not commercially available in the most safe and effective combinations at the time of this writing, but a skilled compounding pharmacist can incorporate compatible agents in preparations designed to ensure best outcomes. Formulations that promote dermal healing are provided for easy reference.


Asunto(s)
Preparaciones Farmacéuticas , Cicatrización de Heridas , Composición de Medicamentos , Humanos , Farmacéuticos , Piel
2.
Int J Pharm Compd ; 25(2): 104-108, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798109

RESUMEN

Active learning is common in pharmacy school. However, such learning strategy rarely integrates more than one specific field. Here, we develop a new active multidisciplinary approach centered on compounded capsule's quality evaluation. Captopril capsules were chosen for their important role to control systemic arterial hypertension, a highly prevalent disease. The study design was developed and demonstrated by two undergraduate students. Four compounding pharmacies were selected randomly, and sixty capsules of captopril 25 mg were purchased from each pharmacy at three different periods (12 batches). The capsules were evaluated according to general aspects (visual observation), label information (according to the Brazilian Pharmacopoeia's regulation), weight variation (standard method), and uniformity of dosage units (iodine titration). All batches met the requirements expected for general aspects and one pharmacy did not meet minimum label criteria. Weight variation out of the standard limits was observed for three of the batches evaluated, and five batches were found to be out of the acceptable captopril's dosage. All stages of this activity resulted in important discussions pertaining to the education of pharmacists. The experimental multidisciplinary approach presented a lead to different discussions on several expertise fields and might have a great impact on the formation of future pharmacist. Several topics could be addressed using this activity, such as analytical chemistry, titration, stoichiometry, medicine preparation, pharmacological risks, et h i c a l aspects, and the pharmacist's role to guarantee health.


Asunto(s)
Farmacias , Farmacia , Brasil , Composición de Medicamentos , Humanos , Farmacéuticos , Estudiantes
3.
Int J Pharm Compd ; 25(2): 115-124, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798111

RESUMEN

The United States Pharmacopeial Convention, Inc. recommends within the standards of the United States Pharmacopeia that compounding pharmacies have staff dedicated to quality assurance and quality control to ensure patients are receiving safe medications. The quality-control program must include testing. While compounding pharmacies have grown familiar with potency, sterility, and endotoxin testing, there are many more tests recommended within the United States Pharmacopeia that are critical for evaluating the quality of compounded preparations. This article discusses when a few of these tests should be utilized, how to assign acceptance criteria, and how test results are obtained.


Asunto(s)
Endotoxinas , Farmacias , Composición de Medicamentos , Humanos , Control de Calidad , Estándares de Referencia , Estados Unidos
4.
Int J Pharm Compd ; 25(2): 126-128, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798112

RESUMEN

Humectants, hygroscopic substances used to minimize water loss and to prevent the drying out of different types of products, are in common use not only in pharmaceuticals but also in foods, cosmetics, etc. The proper selection of a humectant in a pharmaceutical formula depends upon the dosage form, ingredients, physical and chemical characteristics, as well as stability issues. This article discusses the importance of humectants and their applications in pharmaceutics.


Asunto(s)
Excipientes , Higroscópicos , Composición de Medicamentos , Agua
5.
Int J Pharm Compd ; 25(2): 131-139, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798113

RESUMEN

Intravenous admixture compounding is common practice in most hospitals throughout the world, regardless of the country. Compounding intravenous medications involves risk, as there is a high potential for error due to their complexity in compounding, and working in an aseptic environment itself poses issues for the compounder. Part 9-A of this series of articles on the topic of intravenous admixture preparation considerations discusses 1) the background, 2) types of errors, 3) where errors can occur, 4) automated parenteral nutrition compounding systems, 5) accuracy and strength issues, and 6) medication error prevention. Part 9-B of this series of articles will include 1) a discussion on standardization (of both formulas and procedures), 2) competency, 3) compliance, 4) a detailed table on the sources of errors, and 5) the considerations for the prevention of errors.


Asunto(s)
Errores de Medicación , Nutrición Parenteral , Administración Intravenosa , Composición de Medicamentos , Humanos , Errores de Medicación/prevención & control
6.
Int J Pharm Compd ; 25(2): 163-168, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798116

RESUMEN

An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.


Asunto(s)
Nadolol , Jeringas , Administración Oral , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Plásticos , Suspensiones
7.
Int J Pharm Compd ; 25(2): 169-175, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798117

RESUMEN

Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.


Asunto(s)
Metronidazol , Administración Oral , Anciano , Niño , Cromatografía Líquida de Alta Presión , Cromonas , Composición de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Suspensiones
8.
AAPS PharmSciTech ; 22(3): 85, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33650023

RESUMEN

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.


Asunto(s)
Composición de Medicamentos/métodos , Naproxeno/administración & dosificación , Naproxeno/síntesis química , Tecnología Farmacéutica/métodos , Administración Oral , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacocinética , Formas de Dosificación , Liberación de Fármacos , Excipientes/administración & dosificación , Excipientes/síntesis química , Excipientes/farmacocinética , Naproxeno/farmacocinética , Comprimidos
9.
AAPS PharmSciTech ; 22(3): 97, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33694033

RESUMEN

Granule size distribution (GSD) is one of the critical quality attributes in the roller compaction (RC) process. Determination of GSD for newly developed pharmaceutical compounds with unknown ribbon breakage behaviors at the RC milling step requires a quantitative insight into process parameters and ribbon attributes. Despite its pivotal role in mapping the process operating conditions to achieve desired granule size, limited work has been presented in literature with a focus on RC-milling modeling. In this study, a multi-variate mathematical model is presented to simulate the full size-distribution of granulated ribbons as a function of ribbon mechanical properties. Experimental data with a lab-scale oscillating milling apparatus were generated using ribbons made of various powder compositions. Model parameters were determined by fitting it to experimental data sets. Parameters obtained from the first step were correlated to ribbon Young's modulus. The model was validated by predicting GSD of data that were excluded in model development step. Predictive capabilities of the developed model were further explored by simulating GSD profiles of a granulated pharmaceutical excipient obtained at three different conditions of a real-scale Gerteis RC system. While maintaining the milling operating conditions similar to the lab-scale apparatus (i.e., screen size and spacing, and low rotor speed), the proposed modeling approach successfully predicted the GSD of roller compacted MCC powder as the model compound. This model can be alternatively utilized in conjunction with an RC model in order to facilitate the process understanding to obtain granule attributes as part of Quality-by-Design paradigm.


Asunto(s)
Módulo de Elasticidad , Excipientes/síntesis química , Modelos Teóricos , Tamaño de la Partícula , Tecnología Farmacéutica/métodos , Composición de Medicamentos/instrumentación , Excipientes/farmacocinética , Análisis Multivariante , Polvos , Comprimidos , Resistencia a la Tracción
10.
AAPS PharmSciTech ; 22(3): 105, 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33718988

RESUMEN

Medicine regulators require the melting points for crystalline drugs, as they are a test for chemical and physical quality. Many drugs, especially salt-forms, suffer concomitant degradation during melting; thus, it would be useful to know if the endotherm associated with melt degradation may be used for characterising the crystallinity of a powder blend. Therefore, the aim of this study was to investigate whether melt-degradation transitions can detect amorphous content in a blend of crystalline and amorphous salbutamol sulphate. Salbutamol sulphate was rendered amorphous by freeze and spray-drying and blended with crystalline drug, forming standards with a range of amorphous content. Crystalline salbutamol sulphate was observed to have a melt-degradation onset of 198.2±0.2°C, while anhydrous amorphous salbutamol sulphate prepared by either method showed similar glass transition temperatures of 119.4±0.7°C combined. Without the energy barrier provided by the ordered crystal lattice, the degradation endotherm for amorphous salbutamol sulphate occurred 50°C below the melting point, with an onset of 143.6±0.2°C. The enthalpies for this degradation transition showed no significant difference between freeze- and spray-dried samples (p>0.05). Distinct from convention, partial integration of the crystalline melt-degradation endotherm was applied to the region 193-221°C which had no contribution from the degradation of amorphous salbutamol sulphate. The linear correlation of these partial areas with amorphous content, R2=0.994, yielded limits of detection and quantification of 0.13% and 0.44% respectively, independent of drying technique. Melt-degradation transitions may be re-purposed for the measurement of amorphous content in powder blends, and they have potential for evaluating disorder more generally.


Asunto(s)
Albuterol/síntesis química , Albuterol/farmacocinética , Química Farmacéutica/métodos , Broncodilatadores/síntesis química , Broncodilatadores/farmacocinética , Rastreo Diferencial de Calorimetría/métodos , Cristalización/métodos , Composición de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/métodos , Polvos , Temperatura de Transición
11.
AAPS PharmSciTech ; 22(3): 107, 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33719019

RESUMEN

Ophthalmic diseases represent a significant problem as over 2 billion people worldwide suffer from vison impairment and blindness. Eye drops account for around 90% of ophthalmic medications but are limited in success due to poor patient compliance and low bioavailability. Low bioavailability can be attributed to short retention times in the eye caused by rapid tear turnover and the difficulty of drug diffusion through the multi-layered structure of the eye that includes lipid-rich endothelial and epithelial layers as well as the stroma which is high in water content. In addition, there are barriers such as tight junctional complexes in the corneal epithelium, lacrimal turnover, nasolacrimal drainage, blinking reflexes, efflux transporters, drug metabolism by ocular enzymes, and drug binding to or repulsion from conjunctival mucins, tear proteins, and melanin. In order to maximize transport through the cornea while minimizing drug loss through other pathways, researchers have developed numerous methods to improve eye drop formulations including the addition of viscosity enhancers, permeability enhancers, mucoadhesives, and vasoconstrictors, or using formulations that include puncta occlusion, nanocarriers, or prodrugs. This review explains the mechanism behind each of these methods, examines their history, analyzes previous and current research, evaluates future applications, and discusses the pros and cons of each technique.


Asunto(s)
Administración Oftálmica , Composición de Medicamentos/métodos , Soluciones Oftálmicas/síntesis química , Soluciones Oftálmicas/farmacocinética , Animales , Disponibilidad Biológica , Córnea/efectos de los fármacos , Córnea/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Oftalmopatías/tratamiento farmacológico , Oftalmopatías/metabolismo , Humanos , Soluciones Oftálmicas/administración & dosificación , Profármacos/administración & dosificación , Profármacos/síntesis química , Profármacos/farmacocinética , Viscosidad
12.
Int J Nanomedicine ; 16: 1457-1472, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33654396

RESUMEN

Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity. Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model. Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity. Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.


Asunto(s)
Diflunisal/administración & dosificación , Sistemas de Liberación de Medicamentos , Emulsiones/química , Nanogeles/química , Polietilenglicoles/química , Polietileneimina/química , Administración Tópica , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Carragenina , Diflunisal/química , Diflunisal/farmacología , Diflunisal/uso terapéutico , Modelos Animales de Enfermedad , Composición de Medicamentos , Liberación de Fármacos , Edema/tratamiento farmacológico , Edema/patología , Conductividad Eléctrica , Concentración de Iones de Hidrógeno , Masculino , Tamaño de la Partícula , Permeabilidad , Transición de Fase , Ratas , Piel/efectos de los fármacos , Absorción Cutánea/efectos de los fármacos , Solubilidad , Tensoactivos/química , Viscosidad
13.
Pharm Res ; 38(3): 473-478, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33660201

RESUMEN

The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA (mRNA)-based vaccines have become the front-runners because of their safety profiles, precise and reproducible immune response with more cost-effective and faster production than other types of vaccines. However, the physicochemical properties of naked mRNA necessitate innovative delivery technologies to ferry these 'messengers' to ribosomes inside cells by crossing various barriers and subsequently induce an immune response. Intracellular delivery followed by endosomal escape represents the key strategies for cytoplasmic delivery of mRNA vaccines to the target. This Perspective provides insights into how state-of-the-art nanotechnology helps break the delivery barriers and advance the development of mRNA vaccines. The challenges remaining and future perspectives are outlined.


Asunto(s)
/uso terapéutico , Citoplasma/metabolismo , Portadores de Fármacos , Lípidos/química , Nanopartículas , Ribosomas/metabolismo , Vacunas Sintéticas/uso terapéutico , Animales , /virología , /farmacocinética , Composición de Medicamentos , Humanos , Nanomedicina , Vacunas Sintéticas/química
14.
Food Chem ; 351: 129315, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-33647686

RESUMEN

Mangiferin-loaded nanobilosomes (MGF-NBSs) were developed using microfluidic-based techniques to improve aqueous solubility, digestive stability, and cellular antioxidant activity (CAA) of mangiferin. Preliminary experiments showed that optimal formation conditions were 5:1 aqueous (water) to solvent (ethanol) phase ratio and 85 mL/min total flow rate. Further optimization using response surface methodology provided the optimal formulation (200 mg encapsulant consisting of 90.91% phosphatidylcholine and 9.09% sodium glycocholate, and 25.89 mg mangiferin), achieving 9.25% mangiferin loading and 80.65% encapsulation efficiency. Mono-dispersed MGF-NBSs with an average size of around 48.14 nm and zeta potential of -30.1 mV were obtained. FTIR and DSC results confirmed the successful encapsulation of mangiferin into the nanobilosomes and revealed interactions among the components. MGF-NBSs showed a 7-fold increase in the aqueous solubility compared with non-encapsulated mangiferin. CAA of MGF-NBSs in Caco-2 cells was 2 times higher than that of mangiferin and the in vitro digestive stability was improved.


Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Nanoestructuras/química , Agua/química , Xantonas/química , Xantonas/farmacología , Antioxidantes/metabolismo , Células CACO-2 , Digestión , Composición de Medicamentos , Humanos , Dispositivos Laboratorio en un Chip , Tamaño de la Partícula , Solubilidad , Xantonas/metabolismo
15.
Int J Nanomedicine ; 16: 1977-1992, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727810

RESUMEN

Background: Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges. Aim: To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols. Methods: Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated. Results: The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (-23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines. Conclusion: Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular diseases.


Asunto(s)
Composición de Medicamentos , Ésteres/química , Hipercolesterolemia/tratamiento farmacológico , Lípidos/química , Nanopartículas/química , Fitosteroles/uso terapéutico , Muerte Celular , Emulsiones/química , Endocitosis , Citometría de Flujo , Células HT29 , Células Hep G2 , Humanos , Tamaño de la Partícula , Polvos , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Temperatura
16.
Int J Nanomedicine ; 16: 2013-2044, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727812

RESUMEN

Background: Sulpiride (SUL), is a selective antidopaminergic drug that had extensive biological activities. However, its sparingly aqueous solubility and limited gastrointestinal permeability lead to scanty oral bioavailability which hinders its clinical efficacy. Objective: SUL-loaded lipospheres (SUL-LPS) were designed to serve as an oral biocompatible nanovector for improving SUL permeability as well as conquering its low oral absorption and then in turn enhancing its antidepressant action. Methods: SUL-LPS were fabricated via two processing techniques namely, melt emulsification and solvent evaporation. The impact of different lipid cores, phospholipid shells together with various surfactant concentrations and types on the lipospheres properties were screened. Detailed physicochemical elucidations were performed followed by ex vivo permeation appraisal using the non-everted intestine model. The pharmacokinetic parameters of SUL-LPS, free SUL and marketed product were assessed following oral administration to healthy rats. Reserpine-induced depression rat model was used to assess the antidepressant action of SUL-LPS on which full behavioural and biochemical analysis was conducted. Safety attributes of nanoencapsulated SUL on the brain and other internal organs were evaluated. Results: The optimum LPS revealed an excellent nanosize with a narrow PdI, negative zeta potential and acceptable entrapment efficiency of 68.62 nm, 0.242, -30.4 mV and 84.12%, respectively. SUL-LPS showed a sustained release pattern and 2.1-fold enhancement in the intestinal permeation parameters with low mucin interaction. Oral pharmacokinetic appraisal exhibited that LPS provided 3.4-fold improvement in SUL oral bioavailability together with long-circulating properties, relative to the free drug. Pharmacodynamic study confirmed the superior antidepressant action of SUL-LPS as evident by 1.6 and 1.25-fold elevation in the serotonin and dopamine expressions, respectively. Meanwhile, nanotoxicological appraisal proved the biocompatibility of SUL-LPS upon repetitive oral administration. Conclusion: Rationally designed lipospheres hold promising in vitro and in vivo characteristics for efficient delivery of SUL with high oral bioavailability, antidepressant activity together with a good safety profile.


Asunto(s)
Antidepresivos/farmacología , Lípidos/química , Nanopartículas/química , Sulpirida/administración & dosificación , Sulpirida/farmacología , Administración Oral , Animales , Materiales Biocompatibles/química , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Liberación de Fármacos , Liofilización , Masculino , Mucinas/química , Nanopartículas/ultraestructura , Neurotransmisores/metabolismo , Especificidad de Órganos/efectos de los fármacos , Tamaño de la Partícula , Permeabilidad , Ratas Sprague-Dawley , Ratas Wistar , Sulpirida/química , Sulpirida/farmacocinética , Porcinos
17.
AAPS PharmSciTech ; 22(3): 102, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712901

RESUMEN

Sceletium tortuosum is one of the most promising medicinal plant species for treating anxiety and depression. Traditionally, aerial parts are chewed (masticatory herbal medicine) providing fast relief and rendering the masticatory route for delivery, ideal. This study intended formulating novel medicated chewing gum containing S. tortuosum to alleviate depression and anxiety. S. tortuosum extract was formulated into directly compressed medicated chewing gum (MCG) containing different Health-in-Gum® (HIG) bases through process optimization with the SeDeM Diagram Expert System. Physical properties of MCGs were characterized, and specialized drug release studies performed. According to the manufacturer, only HIG-03 was specifically developed for direct compression; however, the SeDeM System was successfully applied to all HIG-bases investigated. HIG-01 and HIG-04 are also considered useful in direct compression as no considerable differences in these MCG formulations' physical properties were recognized. Inclusion of a lubricant, however, is deemed essential, and MCG comprising HIG-01, most suited for direct compression. Dissolution experiments found only two alkaloids used as markers, mesembrine and mesembrenone, were released in quantifiable concentrations regardless formulation constituents. Novel directly compressed MCG-containing S. tortuosum extract was successfully formulated by which the biologically active phytochemicals of S. tortuosum can be scientifically delivered through the traditionally applied mastication method.


Asunto(s)
Aizoaceae/química , Ansiolíticos/administración & dosificación , Antidepresivos/administración & dosificación , Goma de Mascar , Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Composición de Medicamentos , Liberación de Fármacos , Excipientes , Sistemas Especialistas , Lubricantes , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Polvos
18.
AAPS PharmSciTech ; 22(3): 103, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33712964

RESUMEN

The topical use of rosmarinic acid (RA) in skin inflammatory pathologies is restricted due to its poor water solubility, poor permeability, and chemical instability. In this study, RA-loaded transethosomes-in-Carbopol® formulations have been developed to evaluate its anti-inflammatory activity on imiquimod-induced psoriasis-like skin inflammation in mice. In vitro release profiles demonstrated sustained behavior due to the retentive action of gel and the entrapment of RA into the vesicles. However, the low viscosity of the combined formulation increased the drug release rate. Animal evaluation of anti-inflammatory activity demonstrated that transethosomes-in-gel containing dexamethasone (Dex-TE-Gel), as positive control, showed effect in all the pro-inflammatory parameters evaluated, evidencing that these drug-loaded nanocarriers have been effectively reached the site of action. In addition, transethosomes-in-gel containing RA (RA-TE-Gel) formulations produced a great reduction in the punch edema (P < 0.001) and in TNF-α and IL-6 (P < 0.05). However, non-significant differences were obtained for IL-1ß, IL17, and MPO. Despite the protecting effect of Carbopol® and transethosomes on oxidation index and antioxidant activity of RA over the 7 days of treatment, however, a degradation process of this antioxidant to caffeic acid may be the cause of these in vivo results. We have also checked that the pH existing into the intercellular space of damaged cells (pH 6.8) may be affecting. Therefore, our results suggest that RA-TE-Gel could act as an effective RA formulation for skin delivery; further studies will help to understand the loss of activity at the cellular level.


Asunto(s)
Cinamatos/administración & dosificación , Cinamatos/uso terapéutico , Depsidos/administración & dosificación , Depsidos/uso terapéutico , Psoriasis/tratamiento farmacológico , Administración Cutánea , Animales , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Portadores de Fármacos , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Geles , Ratones , Ratones Endogámicos BALB C , Viscosidad
19.
AAPS PharmSciTech ; 22(3): 112, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33748914

RESUMEN

Telmisartan (TLM) is a potent antihypertensive drug with pH-dependent aqueous solubility. This work aimed to enhance the solubility and dissolution rate of TLM by the co-amorphous drug amino acid (AA) approach by combining TLM, with different types and ratios of AAs. The co-amorphous TLM-AA blends were prepared by freeze-drying and investigated for solid-state characteristics like the dissolution rate enhancement of TLM. Among the prepared co-amorphous formulations, TLM-arginine (ARG) exhibited the greatest enhancement in solubility with increasing the molar ratio of ARG. The TLM-ARG at 1:2 ratio showed about a 57-fold increase in solubility of TLM and the highest dissolution percentage in phosphate buffer (pH7.5) (100% in 20 minutes) compared to both crystalline TLM (20% in 60 min) and physical mixture. Powder XRD, DSC, FTIR analysis and SEM demonstrated the formation of amorphous form within the co-amorphous formulations. Only TLM:ARG (1:0.5) were stable at (40°C, 75% RH) for a minimum of 90 days. In conclusion, ARG was able to stabilize the amorphous form of TLM and enhances its aqueous solubility and dissolution. The 1:2 w/w ratio of TLM-ARG co-amorphous showed the best solubility and dissolution rate while the 1:0.5 w/w ratio showed the best stability.


Asunto(s)
Aminoácidos/química , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Telmisartán/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/química , Tampones (Química) , Rastreo Diferencial de Calorimetría , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Solubilidad , Telmisartán/química , Difracción de Rayos X
20.
AAPS PharmSciTech ; 22(3): 98, 2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33709195

RESUMEN

The U.S. Food and Drug Administration (FDA) emphasizes drug product development by Quality by Design (QbD). Critical material attributes (CMAs) are a QbD element that has an impact on pharmaceutical operations and product quality. Pharmaceutical drugs often crystallize as needle-shaped (a CMA) particles and affect the process due to poor flowability, low bulk density, and high compressibility, and eventually the product performance. In this study, the product obtained from crystallization was needle-shaped Ciprofloxacin HCl (CIPRO), formed lumps during drying, and compacted during processing through feeders. To delump small amounts of materials and break the needles, multiple available devices (mortar-pestle, Krups grinder) and custom-made grinder were assessed before formulation. The processed CIPRO powder was then used to make tablets in the miniature tablet manufacturing unit developed by the team at MIT. The critical quality attributes (CQA) of the tablets, set by the United States Pharmacopeia (USP), were then assessed for the drug powder processed with each of these devices. Powder properties comparable to commercial CIPRO were obtained when the custom MIT-designed grinder was used, leading to tablets that meet the USP criteria, with comparable dissolution profiles of those for marketed CIPRO tablets. This study demonstrates how needle-shaped crystals have an impact on pharmaceutical operations, even if it is on a miniature scale, and how proper shape and subsequent flow properties can be obtained by processing the particles through the MIT team-designed grinder.


Asunto(s)
Química Farmacéutica/métodos , Ciprofloxacino/síntesis química , Tamaño de la Partícula , Tecnología Farmacéutica/métodos , Cristalización/métodos , Desecación , Composición de Medicamentos/métodos , Polvos , Comprimidos
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