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1.
Talanta ; 236: 122825, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635215

RESUMO

Relative matrix effects between an ambient mass spectrometric technique known as coated blade spray (CBS) and liquid chromatographic separation approach when applied to multiresidue pesticide analysis in strawberry samples are explored. Acceptable slope relative standard deviations (RSD <15 %) were observed for the 9 compounds under study for both CBS-MS/MS (2.2-12.6 %) and LC-MS/MS (2.8-12.9 %) approaches. The findings signify both the elimination of relative matrix effects with the sample preparation and matrix match calibration with internal standard correction methods employed along with no matrix effect compromise made when using the direct-to-MS approach. Similarly, slopes of pesticides spiked from commercially available formulations (containing one or two pesticides) were found to not differ significantly from slopes generated with multiresidue pesticide standards (containing 24 additional pesticides besides the target 9 analytes) with either technique, highlighting the resistance of the employed methods to the excipients present in pesticide formulations in large amounts.


Assuntos
Fragaria , Resíduos de Praguicidas , Praguicidas , Cromatografia Líquida , Excipientes , Resíduos de Praguicidas/análise , Espectrometria de Massas em Tandem
2.
Int J Pharm Compd ; 25(5): 396-400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34623966

RESUMO

Many drugs inherently have a taste associated with them when in solution; these are the innate or inherent tastes associated with the drug itself and are often included in the official United States Pharmacopeia-National Formulary description of the drug. Some drugs will induce a taste or a change in taste characteristics when administered to a patient; these are induced tastes and a long list of examples is included in this article. Oftentimes, it is necessary to alter the properties of a dosage form to overcome disagreeable tastes of drugs through the use of different flavoring methods, which is also discussed. Patient compliance is critical for effective therapy and taste is important for compliance.


Assuntos
Excipientes , Paladar , Composição de Medicamentos , Aromatizantes , Humanos
3.
Mater Sci Eng C Mater Biol Appl ; 129: 110211, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579874

RESUMO

In part 1, we have investigated drug release by solid-solution single fibers comprising a sparingly water-soluble drug (ibuprofen) and a highly water-soluble dual excipient (low-molecular-weight hydroxypropyl methyl cellulose (HPMC) and polyoxyl stearate (POS)). In this part, fibrous dosage forms of the same formulation are prepared by 3D-micro-patterning, tested, and modeled. Upon immersion in a small volume of dissolution fluid, the dosage forms rapidly swelled and formed a low-viscosity medium, which subsequently dissolved. The dissolution time increased slightly with volume fraction of the fibers, φs, in the solid dosage form, but was less than 25 minutes even up to φs = 0.65. After dosage form dissolution, the fluid was supersaturated by a factor of two; the drug concentration then gradually decreased to solubility. The solubility was proportional to the concentration of POS, and was enhanced by a factor of six at φs = 0.65 (the most densely-packed dosage form). Theoretical models suggest that the dissolution fluid percolates the contiguous void space almost immediately, and the HPMC-POS fibers expand isotropically as water diffuses in. Because the void space remains contiguous in isotropic expansion, the dissolution fluid continues to percolate through and diffuse into the fibers. Thus, even the densely-packed dosage forms form a low-viscosity medium that deforms and dissolves rapidly. Consequently, the solid-solution fibrous dosage forms enable enhanced release rate, supersaturation, and solubility of sparingly-soluble drugs.


Assuntos
Preparações Farmacêuticas , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes , Derivados da Hipromelose , Solubilidade
4.
J Pharm Biomed Anal ; 205: 114336, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34492454

RESUMO

This paper proposes a novel image-based approach to detect counterfeit medicines and identify the most relevant regions of the tablet in the task of classification. Images of medicine tablets undergo an initial pre-processing step which (i) removes the background to find the region of interest, (ii) clusters individual pixels into super-pixels, and (iii) extracts features containing color and texture information. The classification relying on Support Vector Machine (SVM) defines the class the respective image will be inserted into. The task of identifying the relevant regions of the tablets for counterfeiting detection is performed using the concept of support vectors, generating a heat map that indicates the regions that contribute the most to the classification purpose. Two datasets containing images of authentic and counterfeit tablets of Cialis and Viagra were used to validate our propositions, achieving correct classification rates of 100% on both datasets. Regarding the task of identifying the most relevant regions, our proposition outperformed the traditional LIME (Local Interpretable Model-agnostic Explanations) method by yielding more robust explanations.


Assuntos
Medicamentos Falsificados , Excipientes , Citrato de Sildenafila , Comprimidos , Tadalafila
5.
Biomater Sci ; 9(20): 6787-6794, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34528030

RESUMO

Coating modification such as drug-eluting coating is one of the most important approaches for the functionalization of biomedical devices. However, the throughputs are limited in conventional coating methods and the concept of miniaturization is rarely fulfilled. A droplet microarray (DMA), as a unique high-throughput platform, can avoid cross-contamination and reduce the consumption of materials which is inherently suitable for coating research yet is difficult to apply with coating materials via traditional methods. Here, we bring up a facile method based on ultrasonic spray deposition to integrate coating materials into a DMA. Several common polymer materials were selected to fabricate a DMA, and the obtained DMA showed the ability to anchor water droplets and form specific patterns. Coating arrays with a typical sandwich structure were also prepared for the high-throughput screening of drug-eluting coatings to demonstrate the potential of the platform in coating research. This developed method is efficient and compatible and enriches the choices of materials that can be applied in DMAs.


Assuntos
Ensaios de Triagem em Larga Escala , Ultrassom , Liberação Controlada de Fármacos , Excipientes , Polímeros , Água
6.
Polim Med ; 51(1): 25-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34505758

RESUMO

BACKGROUND: The pH of the skin surface is usually between 5.4 and 5.9 and functions as a barrier against bacteria and fungi; thus, the composition of the topically applied drug form may be of high importance for proper medication. OBJECTIVES: To evaluate the influence of the measurement conditions in aqueous solutions of ointments, creams, and gels, which include polymeric components, on the pH and conductivity results. MATERIAL AND METHODS: The pH and electrolytic conductivity of aqueous dispersions of commercially available ointments, creams and gels were tested and compared to reference vehicles. RESULTS: The results of the dilution method measurements of the pH and electrolytic conductivity of the ointment preparations are highly diverse, ranging from 5.88 to 6.27, whereas the reference pH for Unguentum simplex was between 5.40 and 5.43. Furthermore, the measurements of the pH and electrolytic conductivity with the dilution method for creams did not provide repeatable results with a small sample size, and the pH of commercial preparations was in the range between 5.79 and 6.37, compared to the reference pH of 5.23-5.46. However, the dilution method for measurements of the pH and electrolytic conductivity was suitable for hydrogel preparations and the obtained results were repeatable in the range of 6.11-6.90, while the reference preparations were in the range of 5.19-5.62. CONCLUSIONS: Evaluation methods of the electrolytic conductivity and pH of the preparations applied on the skin should be further evaluated; however, the pH of the commercial preparation seems to differ from the physiological skin pH, which covers the range of reference preparations.


Assuntos
Excipientes , Polímeros , Géis , Concentração de Íons de Hidrogênio , Pomadas
7.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3764-3771, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472248

RESUMO

The purpose of the present study was to investigate the relationship of the classification of traditional Chinese medicine(TCM) materials with the suitable binder concentration and dosage in the preparation of personalized water-paste pills and establish a model for predicting the binder concentration and dosage. Five representative TCM materials were selected, followed by mixture uniform design. The water-paste pills were prepared by extrusion and spheronization with hypromellose E5(HPMC E5) as the binder. The quality of intermediates and final products was evaluated, and the resulting data were subjected to multivariate statistical analysis. The prediction models for binder concentration and dosage were established as follows: binder concentration: Y_1=0.378 6 + 0.570 1X_A + 2.271 2X_B-0.894 5X_C-0.458 2X_D-1.145 4X_E(when Y_1 < 0, 10% HPMC E5 was required; when Y_1 > 0, 20% HPMC E5 was required), with the accuracy reaching up to 100%; binder dosage: Y_2=32.38 + 0.25X_A + 1.85X_B-0.013X_B~2-0.002 5X_C~2(R~2=0.932 6, P < 0.001). The results showed that the binder concentration and dosage were correlated positively with the proportion of fiber material but negatively with the proportions of sugar material and brittle material. Then the validation experiments were conducted with the prediction models and all the prescriptions could be successfully prepared at one time. These demonstrated that following the classification of TCM materials and the calculation of their proportions in the prescription, the established mathematical model could be adopted for predicting the binder concentration and dosage required in the preparation of personalized water-paste pills, which contributed to reducing the pre-formulation research and guiding the actual production of personalized water-paste pills.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Excipientes , Derivados da Hipromelose , Água
8.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3772-3779, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472249

RESUMO

To explore the correlation between concentrate viscosity and molding quality of personalized traditional Chinese medicine(TCM) condensed water pill, this study established a concentrate viscosity characterization method with rotational rheometry. Seven model prescriptions were respectively concentrated to different degrees and the viscosity of each concentrate was determined. The pre-sence of 'viscosity jump' in the middle stage of 'flag hanging' of all the model prescriptions implied that there might be an ideal viscosity range in the preparation of condensed water pill. The further study of 22 model prescriptions demonstrated that the optimum viscosity range of concentrate was 5-15 Pa·s(25 ℃) for approximately 82% of the prescriptions. About 18% of the prescriptions had a wide range, which might be caused by the high proportions of mineral and crustacean drugs in the crushing part and sugar and fibrous drugs in the decocting part. This study clarified the optimum viscosity range for concentrates of personalized TCM condensed water pills and achieved a preparation technology without any excipient, laying a foundation for the on-line control of the preparation.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Excipientes , Viscosidade , Água
9.
ACS Appl Mater Interfaces ; 13(33): 38969-38978, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34399054

RESUMO

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.


Assuntos
Anti-Hipertensivos/química , Doença das Coronárias/tratamento farmacológico , Portadores de Fármacos/química , Excipientes/química , Indóis/química , Polímeros/química , Anti-Hipertensivos/farmacologia , Dioxanos/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Indóis/farmacologia , Metacrilatos/química , Transição de Fase , Poliésteres/química , Impressão Tridimensional , Pirrolidinonas/química , Relação Estrutura-Atividade
10.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445090

RESUMO

In this paper, we present novel well-defined unimolecular micelles constructed a on poly(furfuryl glycidyl ether) core and highly hydrophilic poly(glyceryl glycerol ether) shell, PFGE-b-PGGE. The copolymer was synthesized via anionic ring-opening polymerization of furfuryl glycidyl ether and (1,2-isopropylidene glyceryl) glycidyl ether, respectively. MTT assay revealed that the copolymer is non-cytotoxic against human cervical cancer endothelial (HeLa) cells. The copolymer thanks to furan moieties in its core is capable of encapsulation of nifuratel, a hydrophobic nitrofuran derivative, which is a drug applied in the gynaecology therapies that shows a broad antimicroorganism spectrum. The study shows high loading capacity of the copolymer, i.e., 146 mg of nifuratel per 1 g of copolymer. The load unimolecular micelles were characterized using DLS and TEM microscopy and compared with the reference glyceryl glycerol ether homopolymer sample. The presence of numerous 1,2-diol moieties in the shell of PFGE-b-PGG macromolecules enabled the formation of reversible cross-links with 2-acrylamidephenylboronic acid-based polyacrylamide. The obtained hydrogels were both injectable and self-healable, which was confirmed with a rheological study.


Assuntos
Antifúngicos/química , Antitricômonas/química , Compostos de Epóxi/química , Furanos/química , Glicerol/química , Hidrogéis/química , Nifuratel/química , Polímeros/química , Antifúngicos/administração & dosagem , Antitricômonas/administração & dosagem , Excipientes/química , Éteres de Glicerila/química , Injeções , Nifuratel/administração & dosagem , Solubilidade
11.
Int J Pharm ; 607: 120962, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34339812

RESUMO

Drug-excipient compatibility study is the essential basis for excipient selection at the pre-formulation stage. According to the pharmaceutical Quality by Design (QbD) principles, a comprehensive understanding of the ingredients' physicochemical properties and a theoretical evaluation of the interaction risk between the drugs and excipients are required for conducting rational compatibility experimental design. Currently, there is an urgent need to establish an artificial intelligence system for researchers to easily get through the problem because it is very inconvenient and hard to utilize those drug-excipient incompatibility data scattered in scientific literature. Here, we designed a knowledge-driven expert system named PharmDE for drug-excipient incompatibility risk evaluation. PharmDE firstly developed an information-rich database to store incompatibility data, covering 532 data items from 228 selected articles. Then, 60 drug-excipient interaction rules were created based on our knowledge and formulation research experiences. Finally, the expert system was developed by organically integrating the database searching and rule-based incompatibility risk prediction, which resulted in four main functionalities: basic search of incompatibility database, data matching by similarity search, drug incompatibility risk evaluation, and formulation incompatibility risk evaluation. PharmDE is expected to be a useful tool for drug-excipient compatibility study and accelerate drug formulation design. It is now freely available at https://pharmde.computpharm.org.


Assuntos
Química Farmacêutica , Excipientes , Inteligência Artificial , Estabilidade de Medicamentos , Sistemas Especialistas
12.
Int J Pharm ; 607: 120968, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34358542

RESUMO

The effect of different binders for direct compression on tablet critical quality attributes was investigated. Dicalcium phosphate, lactose and microcrystalline cellulose were used as fillers and combined with ten binders (10, 20 and 30% w/w). Binder properties were linked to tensile strength via partial least square analysis. Tablets containing VA64F and PH105 exhibited the highest tensile strength which was linked to their compaction properties (specific work of compaction, elasticity, cohesion index) and particle size. In contrast, S1500 and E15 exhibited the lowest tensile strength of all binders. Lubrication method influenced the tensile strength as lubricant sensitivity was observed to some extent for all binders. Tensile strength was significantly higher applying external compared to internal lubrication. Fast disintegration was observed for MCC (PH105 and PH200) and starch (S1500 and NMSt) grades, whereas HPC (KEXF and KEF) and E15 resulted in delayed disintegration. Wettability measurements, via determination of contact angle, correlated well with the disintegration behaviour of the binders and can therefore be used as an indicative measurement for tablet disintegration. This study revealed the effect of binder properties, filler type and lubrication method on tablet critical quality attributes. In addition, the potential of dry binder addition for direct compression was highlighted.


Assuntos
Excipientes , Lactose , Lubrificação , Comprimidos , Resistência à Tração
13.
Int J Pharm ; 607: 120970, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34363917

RESUMO

Hydrochlorothiazide (HCT) multiparticulate systems (MPS) were hot melt coated with the binary mixture of tripalmitin (PPP) and polysorbate 65 (PS 65) to gain an immediate release profile. Once, HCT MPS were produced with a constant ratio of PPP/PS 65 (90:10) at three different coating amounts (15, 25, and 60%w/w) and once the PPP/PS 65 ratio was varied on 98:2 and 80:20, by keeping the coating amount at 60%w/w. PS 65 induced the polymorphic transformation of PPP from the α-form to its most stable ß-form right after the hot melt coating (HMC). A release alteration of HCT, either accelerated or decelerated, occurred after the storage under accelerated conditions. The effect of the API core on the lipid lamellar configuration, the thermal behavior of lipid coating, and the effect of PS 65 concentration on the crystal growth of PPP were investigated via X-ray diffraction and DSC. While a low amount of PS 65 was sufficient to promote crystal growth of PPP and resulted in a decelerated release of HCT from the coating, a higher PS 65 concentration favored phase separation of PPP and PS 65 and led to an accelerated release. The increase in PS 65 reinforced the molecular interaction with the lipophilic HCT, reflected in less crystal growth and decelerated release. The knowledge presented in this study supports understanding the instability of binary emulsifier-lipid coating systems, paving the way for developing robust HMC formulations.


Assuntos
Excipientes , Polissorbatos , Cristalização , Temperatura Alta , Solubilidade , Triglicerídeos
14.
Int J Pharm ; 607: 121008, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34391851

RESUMO

This paper presents new machine vision-based methods for indirect real-time quantification of ultralow drug content during continuous twin-screw wet granulation and tableting. Granulation was performed with a solution containing carvedilol (CAR) as API in the ultralow dose range (0.05w/w% in the granule) and the addition of riboflavin (RI) as a coloured tracer. An in-line calibration in the range of 0.047-0.058 w/w% was prepared for the measurement of CAR concentration using colour analysis (CA) and particle size analysis (PSA), and the validation with HPLC resulted in respective relative errors of 2.62% and 2.30% showing great accuracy. To improve the technique, a second in-line calibration was conducted in a broader CAR concentration range of 0.039-0.063 w/w% utilizing only half the amount of RI (0.045 w/w%), while doubling the output of the granulation line to 2 kg/h, producing a relative error of 4.51% and 4.29%, respectively. Finally, it was shown that the CA technique can also be carried on to monitor the CAR content of tablets in the 42-62 µg dose range with a relative error of 5.20%. Machine vision was proven to be a potent indirect method for the in-line, determination and monitoring of ultralow API content during continuous manufacturing.


Assuntos
Excipientes , Tecnologia Farmacêutica , Calibragem , Composição de Medicamentos , Tamanho da Partícula , Comprimidos
15.
Int J Pharm ; 607: 121005, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34391855

RESUMO

Hydrophilic matrices are of utmost interest for oral prolonged release of drugs. However, they show decreasing release rate over time, mainly due to lengthening of the diffusional pathway across the gel formed upon glass-rubber transition of the polymer. Therefore, achievement of zero-order release kinetics, which could reflect in constant drug plasma levels, is still an open issue. With the aim of improving the release performance of hydroxypropyl methylcellulose (HPMC) systems, the use of cellulolytic enzymes was proposed to aid erosion of the swollen matrix, thereby counteracting the release rate decrease particularly toward the end of the process. The effectiveness of this strategy was evaluated by studying the mass loss and drug tracer release from tableted matrices consisting of high-viscosity HPMC (Methocel® K4M), Acetaminophen and increasing amounts (0.5-10% on HPMC) of a cellulolytic product (Sternzym® C13030). A faster erosion and progressive shift to linearity of the overall release profiles were observed as a function of the enzyme concentration. Release was markedly linear from matrices containing 5 and 10% Sternzym® C13030. In partially coated matrices with these cellulase concentrations, such results were in agreement with data of erosion and swelling front movement, which exhibited early and long-lasting synchronization.


Assuntos
Celulase , Excipientes , Química Farmacêutica , Preparações de Ação Retardada , Derivados da Hipromelose , Cinética , Metilcelulose , Solubilidade , Comprimidos
16.
Int J Pharm ; 608: 121033, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34419592

RESUMO

In this study, four low molecular weight (LMW) excipients, tryptophan (TRY), phenylalanine (PHE), lysine (LYS) and saccharin (SAC) were evaluated as co-formers to generate co-amorphous systems (CAMS) by ball milling with carvedilol (CRV). Mixtures of CRV and LMW excipient in 1:0.5, 1:1 and 1:2 drug:excipient molar ratios were ball milled and analysed by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier transform (FT-IR) infrared spectroscopy and dissolution testing. CAMS were formed by milling of a mixture of CRV with TRY in 1:2 M ratio and SAC in 1:1 M ratio, while amorphization of only CRV was achieved in other mixtures with SAC. In other samples containing TRY and PHE, milling resulted in partial amorphization, while LYS was the least suitable excipient for the amorphization of CRV. Unexpectedly, the highest supersaturation of CRV was achieved from samples containing CRV and LYS in 1:1 and 1:2 M ratios, despite the absence of a significant reduction in CRV crystallinity upon milling of these samples. Increase of hydrophobic surface area caused by milling of samples with TRY and PHE and agglomeration during dissolution testing of samples containing SAC are likely causes of poor dissolution performance of mixtures containing fully or partially amorphous CRV.


Assuntos
Excipientes , Varredura Diferencial de Calorimetria , Carvedilol , Composição de Medicamentos , Estabilidade de Medicamentos , Peso Molecular , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
17.
Molecules ; 26(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34361669

RESUMO

Cymbopogon citratus DC (Stapf.) is a perennial grass and it is distributed around the world. It is used as a condiment for food and beverage flavouring in the form of infusions and decoctions of its dried leaves. Our previous studies have shown antioxidant, anti-inflammatory and gastroprotective activities for the infusion and its phenolic fractions. The aim of the present work was to develop oral dosage forms from a Cymbopogon citratus extract to be used as a functional food with antioxidant properties. Initially, an essential oil-free infusion was prepared, lyophilized and characterized by HPLC-PDA. Total phenols were quantified with the Folin-Ciocalteu method and the antioxidant activity was assessed by DPPH assay. Gelatine capsules containing the extract with different excipients, selected after DSC and IR trials, were prepared. A formulation exhibiting better antioxidant behaviour in a gastric environment was attained. These results suggest that the proposed formulation for this extract could be a valuable antioxidant product and, consequently, make an important contribution to "preventing" and minimizing diseases related to oxidative stress conditions.


Assuntos
Antioxidantes/química , Cymbopogon/química , Composição de Medicamentos/métodos , Extratos Vegetais/química , Folhas de Planta/química , Administração Oral , Cápsulas , Cromatografia Líquida de Alta Pressão/métodos , Excipientes/química , Flavonoides/análise , Gelatina/química , Polifenóis/análise , Taninos/análise
18.
J Pharm Biomed Anal ; 205: 114305, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34385017

RESUMO

Raman chemical mapping is an inherently slow analysis tool. Accurate and robust multivariate analysis algorithms, which require least amount of time and effort in method development are desirable. Calibration-free regression and resolution approaches such as classical least squares (CLS) and multivariate curve resolution using alternating least squares (MCR-ALS), respectively, help in reducing the resources required for method development. However, conventional CLS does not consider appropriate constraints, which may result in negative and/or greater than 100 % Raman concentration scores, while MCR-ALS may not always be as accurate as regression-based algorithms. Linear iterative optimization technology (IOT) is another calibration-free algorithm, which with appropriate constraints has previously shown promise in online and offline pharmaceutical mixture composition determination. This paper aims to evaluate the performance of the linear IOT algorithm for Raman chemical mapping of the active pharmaceutical ingredient (API), diluent, and lubricant in pharmaceutical tablets. Two pre-processing strategies were applied to the raw Raman mapping spectra. The results were compared with CLS (current reference method) and MCR-ALS. Special emphasis was given to mapping at low Raman exposure times to enable feasible total acquisition times (< 5 h). The quality of IOT/CLS/MCR-ALS estimated Raman concentration predictions were assessed by calculating a correlation factor between the spectrum corresponding to the maximum predicted concentration (or resolved spectra) of a component for IOT/CLS (or MCR-ALS) and the pure powder component spectrum. The Raman chemical maps were visualized, and the average Raman concentrations scores were compared. The results demonstrated the utility of IOT in Raman chemical mapping of pharmaceutical tablets. The diluent (lactose) and API (semi-fine APAP) used in this study were reliably estimated by IOT at relatively short Raman exposure times. On the other hand, as expected, the lubricant (magnesium stearate) could not be detected in any of the cases investigated here, irrespective of the algorithm used. Overall, for the API and diluent used in this formulation as well as the chemical mapping conditions, linear IOT seemed to better estimate the pure spectrum intensities and the average Raman scores (closer to CLS) in comparison to MCR-ALS. Moreover, application of appropriate constraints in linear IOT avoided the presence of negative and/or greater than 100 % Raman concentration scores, as observed in CLS-based Raman chemical maps.


Assuntos
Excipientes , Preparações Farmacêuticas , Análise dos Mínimos Quadrados , Análise Multivariada , Análise Espectral Raman , Comprimidos , Tecnologia , Tecnologia Farmacêutica
19.
Molecules ; 26(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34361646

RESUMO

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10-30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion.


Assuntos
Liberação Controlada de Fármacos , Naproxeno/química , Impressão Tridimensional , Comprimidos/química , Tecnologia Farmacêutica/métodos , Excipientes/química , Solubilidade , Temperatura
20.
Int J Pharm ; 607: 120956, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34333024

RESUMO

Nowadays, the treatment of health care-associated infections represents a serious issue, due to the increasing number of bacterial strains resistant to traditional antibiotics. The use of antiseptics like quaternary ammonium salts and biguanides is a viable alternative to face these life-threatening infections. However, their inherent toxicity as well as the necessity of providing a sustained release to avoid the formation of pathogen biofilms are compelling obstacles towards their assessment in the hospitals. Within this framework, the role of polymeric drug delivery systems is fundamental to overcome the aforementioned problems. Biocompatibility, biodegradability and excipient-drug interactions are crucial properties determining the efficacy of the formulation. In this work, we provide an in-depth analysis of the polymer drug delivery systems that have been developed or are under development for the sustained release of positively charged antiseptics, highlighting the crucial characteristics that allowed to achieve the most relevant therapeutic effects. We reported and compared natural occurring polymers and synthetic carriers to show their pros and cons and applicability in the treatment of health care-associated infections. Then, the discussion is focused on a particularly relevant class of materials adopted for the scope, represented by polyesters, which gave rise, due to their biodegradability, to the field of resorbable drug delivery devices. Finally, a specific analysis on the effect of the polymer functionalization over the formulation performances for the different types of polymeric carriers is presented.


Assuntos
Anti-Infecciosos Locais , Excipientes , Atenção à Saúde , Sistemas de Liberação de Medicamentos , Polímeros
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