Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 14.248
Filtrar
1.
Sci Rep ; 14(1): 15106, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956156

RESUMO

We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.


Assuntos
Excipientes , Polissorbatos , Excipientes/química , Polissorbatos/química , Vitamina E/química , Tensoativos/química , Pirrolidinas/química , Simulação de Dinâmica Molecular , Termodinâmica , Tecnologia de Extrusão por Fusão a Quente/métodos , Compostos de Vinila
2.
Eur J Pharm Biopharm ; 201: 114380, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38960290

RESUMO

We have used pulsed field gradient (PFG)-NMR diffusion experiments, also known as DOSY, in combination with small angle X-ray scattering measurements to investigate structure and molecular exchange dynamics between pharmaceutical lipid nanoparticles and the bulk phase. Using liposomes and lipoplexes formed after complexation of the liposomes with messenger mRNA as test systems, information on dynamics of encapsulated water molecules, lipids and excipients was obtained. The encapsulated fraction, having a diffusivity similar to that of the liposomes, could be clearly identified and quantified by the NMR diffusion measurements. The unilamellar liposome membranes allowed a fast exchange of water molecules, while sucrose, used as an osmolyte and model solute, showed very slow exchange. Upon interactions with mRNA a topological transition from a vesicular to a lamellar organization took place, where the mRNA was inserted in repeating lipid bilayer stacks. In the lipoplexes, a small fraction of tightly bound water molecules was present, with a diffusivity that was influenced by the additional presence of sucrose. This extended information on dynamic coherencies inside pharmaceutical nanoparticle products, provided by the combined application of SAXS and PFG-NMR diffusion measurements, can be valuable for evaluation of quality and comparability of nanoscaled pharmaceuticals.


Assuntos
Lipossomos , Espectroscopia de Ressonância Magnética , Nanopartículas , RNA Mensageiro , Espalhamento a Baixo Ângulo , Difração de Raios X , Nanopartículas/química , Espectroscopia de Ressonância Magnética/métodos , Difusão , Cinética , Difração de Raios X/métodos , Sacarose/química , Lipídeos/química , Água/química , Excipientes/química , Bicamadas Lipídicas/química
3.
AAPS PharmSciTech ; 25(6): 159, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38987438

RESUMO

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.


Assuntos
Ácido Ascórbico , Química Farmacêutica , Estabilidade de Medicamentos , Ácido Ascórbico/química , Química Farmacêutica/métodos , Tartaratos/química , Ácido Cítrico/química , Composição de Medicamentos/métodos , Excipientes/química
4.
Sci Rep ; 14(1): 15631, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972872

RESUMO

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.


Assuntos
Excipientes , Intolerância à Lactose , Lactose , Hipersensibilidade a Leite , Humanos , Excipientes/efeitos adversos , Excipientes/química , Hipersensibilidade a Leite/epidemiologia , Animais , Lactose/efeitos adversos , Lactose/análise , Lactose/química , Bovinos , Proteínas do Leite/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/análise , Alérgenos/análise , Portugal , Laticínios/análise , Laticínios/efeitos adversos
5.
AAPS PharmSciTech ; 25(6): 152, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954218

RESUMO

Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.


Assuntos
Química Farmacêutica , Diarilquinolinas , Lipídeos , Nanopartículas , Tamanho da Partícula , Diarilquinolinas/química , Diarilquinolinas/administração & dosagem , Nanopartículas/química , Lipídeos/química , Química Farmacêutica/métodos , Excipientes/química , Liberação Controlada de Fármacos , Antituberculosos/administração & dosagem , Antituberculosos/química , Composição de Medicamentos/métodos , Difração de Raios X/métodos , Microscopia Eletrônica de Varredura/métodos , Portadores de Fármacos/química , Administração Oral , Lipossomos
6.
AAPS PharmSciTech ; 25(6): 155, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960983

RESUMO

Gummy formulations are considered suitable alternatives to traditional oral dosage forms like tablets and capsules due to their merits that include chewability, softness/flexibility, improved drug release, administration without water, appealing organoleptic properties, better patient compliance, easy preparation and usefulness for persons of different ages (e.g. children). Though there is increasing interest in gummy formulations containing drugs, measurable parameters, and specification limits for evaluating their quality are scarce. Quality check forms an essential part of the pharmaceutical development process because drug products must be distributed as consistently stable, safe, and therapeutically effective entities. Consequently, some quality parameters that could contribute to the overall performance of typical gummy formulations were investigated employing six brands of non-medicinal gummies as specimens. Accordingly, key physicochemical and micromechanical characteristics namely adhesiveness (0.009 - 0.028 mJ), adhesive force (0.009 - 0.055 N), chewiness (2.780 - 6.753 N), cohesiveness (0.910 - 0.990), hardness (2.984 - 7.453 N), springiness (0.960 - 1.000), and resilience (0.388 - 0.572), matrix firmness - compression load (2.653 - 6.753 N) and work done (3.288 - 6.829 mJ), rupture (5.315 - 29.016 N), moisture content (< 5%), weight uniformity (< 2.5 g; < 7.5% deviation), and intraoral dissolution pH (≥ 3.5 ≤ 6.8) were quantified to identify measures that may potentially function as specification limits and serve as prospective reference points for evaluating the quality of gummy formulations. Findings from this work contribute to ongoing efforts to standardize the quality control strategies for gummy formulations, particularly those intended for oral drug delivery.


Assuntos
Composição de Medicamentos , Composição de Medicamentos/métodos , Composição de Medicamentos/normas , Química Farmacêutica/métodos , Química Farmacêutica/normas , Comprimidos/química , Dureza , Administração Oral , Liberação Controlada de Fármacos , Excipientes/química , Adesividade , Controle de Qualidade
7.
AAPS PharmSciTech ; 25(6): 154, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961012

RESUMO

Berberine is used in the treatment of metabolic syndrome and its low solubility and very poor oral bioavailability of berberine was one of the primary hurdles for its market approval. This study aimed to improve the solubility and bioavailability of berberine by preparing pellet formulations containing drug-excipient complex (obtained by solid dispersion). Berberine-excipient solid dispersion complexes were obtained with different ratios by the solvent evaporation method. The maximum saturation solubility test was performed as a key factor for choosing the optimal complex for the drug-excipient. The properties of these complexes were investigated by FTIR, DSC, XRD and dissolution tests. The obtained pellets were evaluated and compared in terms of pelletization efficiency, particle size, mechanical strength, sphericity and drug release profile in simulated media of gastric and intestine. Solid-state analysis showed complex formation between the drug and excipients used in solid dispersion. The optimal berberine-phospholipid complex showed a 2-fold increase and the optimal berberine-gelucire and berberine-citric acid complexes showed more than a 3-fold increase in the solubility of berberine compared to pure berberine powder. The evaluation of pellets from each of the optimal complexes showed that the rate and amount of drug released from all pellet formulations in the simulated gastric medium were significantly lower than in the intestine medium. The results of this study showed that the use of berberine-citric acid or berberine-gelucire complex could be considered a promising technique to increase the saturation solubility and improve the release characteristics of berberine from the pellet formulation.


Assuntos
Berberina , Química Farmacêutica , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes , Tamanho da Partícula , Solubilidade , Berberina/química , Berberina/administração & dosagem , Berberina/farmacocinética , Excipientes/química , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Disponibilidade Biológica , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Pós/química , Difração de Raios X/métodos , Varredura Diferencial de Calorimetria/métodos
8.
AAPS PharmSciTech ; 25(6): 138, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890193

RESUMO

Unexpected cross-contamination by foreign components during the manufacturing and quality control of pharmaceutical products poses a serious threat to the stable supply of drugs and the safety of customers. In Japan, in 2020, a mix-up containing a sleeping drug went undetected by liquid chromatography during the final quality test because the test focused only on the main active pharmaceutical ingredient (API) and known impurities. In this study, we assessed the ability of a powder rheometer to analyze powder characteristics in detail to determine whether it can detect the influence of foreign APIs on powder flow. Aspirin, which was used as the host API, was combined with the guest APIs (acetaminophen from two manufacturers and albumin tannate) and subsequently subjected to shear and stability tests. The influence of known lubricants (magnesium stearate and leucine) on powder flow was also evaluated for standardized comparison. Using microscopic morphological analysis, the surface of the powder was observed to confirm physical interactions between the host and guest APIs. In most cases, the guest APIs were statistically detected due to characteristics such as their powder diameter, pre-milling, and cohesion properties. Furthermore, we evaluated the flowability of a formulation incorporating guest APIs for direct compression method along with additives such as microcrystalline cellulose, potato starch, and lactose. Even in the presence of several additives, the influence of the added guest APIs was successfully detected. In conclusion, powder rheometry is a promising method for ensuring stable product quality and reducing the risk of unforeseen cross-contamination by foreign APIs.


Assuntos
Contaminação de Medicamentos , Pós , Reologia , Pós/química , Reologia/métodos , Contaminação de Medicamentos/prevenção & controle , Excipientes/química , Acetaminofen/química , Celulose/química , Preparações Farmacêuticas/química , Controle de Qualidade , Aspirina/química , Química Farmacêutica/métodos , Lactose/química , Composição de Medicamentos/métodos , Lubrificantes/química , Princípios Ativos
9.
AAPS PharmSciTech ; 25(5): 128, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844721

RESUMO

In this paper, we report two Accelerated Stability Assessment Program (ASAP) studies for a pediatric drug product. Whereas the first study using a generic design failed to establish a predictive model, the second one was successful after troubleshooting the first study and customizing the study conditions. This work highlighted important lessons learned from designing an ASAP study for formulations containing excipients that could undergo phase change at high humidity levels. The stability predictions by the second ASAP model were consistent with available long-term stability data of the drug product under various storage conditions in two different packaging configurations. The ASAP model was part of the justifications accepted by the health authority to submit a stability package with reduced long-term stability data from the primary stability batches for a Supplemental New Drug Application (sNDA).


Assuntos
Química Farmacêutica , Estabilidade de Medicamentos , Excipientes , Excipientes/química , Química Farmacêutica/métodos , Umidade , Armazenamento de Medicamentos , Embalagem de Medicamentos/métodos , Embalagem de Medicamentos/normas , Composição de Medicamentos/métodos , Humanos , Criança , Preparações Farmacêuticas/química , Pediatria/métodos
10.
AAPS PharmSciTech ; 25(5): 127, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844724

RESUMO

The success of obtaining solid dispersions for solubility improvement invariably depends on the miscibility of the drug and polymeric carriers. This study aimed to categorize and select polymeric carriers via the classical group contribution method using the multivariate analysis of the calculated solubility parameter of RX-HCl. The total, partial, and derivate parameters for RX-HCl were calculated. The data were compared with the results of excipients (N = 36), and a hierarchical clustering analysis was further performed. Solid dispersions of selected polymers in different drug loads were produced using solvent casting and characterized via X-ray diffraction, infrared spectroscopy and scanning electron microscopy. RX-HCl presented a Hansen solubility parameter (HSP) of 23.52 MPa1/2. The exploratory analysis of HSP and relative energy difference (RED) elicited a classification for miscible (n = 11), partially miscible (n = 15), and immiscible (n = 10) combinations. The experimental validation followed by a principal component regression exhibited a significant correlation between the crystallinity reduction and calculated parameters, whereas the spectroscopic evaluation highlighted the hydrogen-bonding contribution towards amorphization. The systematic approach presented a high discrimination ability, contributing to optimal excipient selection for the obtention of solid solutions of RX-HCl.


Assuntos
Química Farmacêutica , Excipientes , Polímeros , Cloridrato de Raloxifeno , Solubilidade , Difração de Raios X , Polímeros/química , Excipientes/química , Cloridrato de Raloxifeno/química , Análise Multivariada , Difração de Raios X/métodos , Química Farmacêutica/métodos , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Microscopia Eletrônica de Varredura/métodos , Ligação de Hidrogênio , Cristalização/métodos
11.
AAPS PharmSciTech ; 25(5): 134, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862663

RESUMO

Inclusion complexes require higher concentration of Beta cyclodextrins (ßCD) resulting in increased formulation bulk, toxicity, and production costs. This systematic review offers a comprehensive analysis using Quality by design (QbD) as a tool to predict potential applications of Polyvinylpyrrolidone (PVP) as a ternary substance to address issues of inclusion complexes. We reviewed 623 documents from 2013 to 2023 and Eighteen (18) research papers were selected for statistical and meta-analysis using the QbD concept to identify the most critical factors for selecting drugs and effect of PVP on inclusion complexes. The QbD analysis revealed that Molecular weight (MW), Partition coefficient (Log P), and the auxiliary substance ratio directly affected complexation efficiency (CE), thermodynamic stability in terms of Gibbs free energy (ΔG), and percent drug release. However, Stability constant (Ks) remained unaffected by any of these parameters. The results showed that low MW (250), median Log P (6), and a ßCD: PVP ratio of 2:3 would result in higher CE, lower G, and improved drug release. PVP improves drug solubility, enhances delivery and therapeutic outcomes, and counteracts increased drug ionization due to decreased pH. In certain cases, its bulky nature and hydrogen bonding with CD molecules can form non-inclusion complexes. The findings of the study shows that there is potential molecular interaction between PVP and ß-cyclodextrins, which possibly enhances the stability of inclusion complexes for drug with low MW and log P values less than 9. The systematic review shows a comprehensive methodology based on QbD offers a replicable template for future investigations into drug formulation research.


Assuntos
Ciclodextrinas , Povidona , Solubilidade , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Química Farmacêutica/métodos , Ciclodextrinas/química , Liberação Controlada de Fármacos , Excipientes/química , Peso Molecular , Projetos Piloto , Povidona/química , Termodinâmica
12.
Se Pu ; 42(6): 581-589, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38845519

RESUMO

Oils and fats are commonly used in the pharmaceutical industry as solvents, emulsifiers, wetting agents, and dispersants, and are an important category of pharmaceutical excipients. Fatty acids with unique compositions are important components of oil pharmaceutical excipients. The Chinese Pharmacopoeia provides clear descriptions of the fatty acid types and limits suitable for individual oil pharmaceutical excipient. An unqualified fatty acid composition or content may indicate adulteration or deterioration. The fatty acid composition, as a key indicator for the identification and adulteration evaluation of oil pharmaceutical excipients, can directly affect the quality and safety of oil pharmaceutical excipients and preparations. Gas chromatography is the most widely used technique for fatty acid analysis, but it generally requires derivatization, which affects quantitative accuracy. Supercritical fluid chromatography (SFC), an environmentally friendly technique with excellent separation capability, offers an efficient method for detecting fatty acids without derivatization. Unlike other chromatographic methods, SFC does not use nonvolatile solvents (e. g., water) as the mobile phase, rendering it compatible with an evaporative light-scattering detector (ELSD) for enhanced detection sensitivity. However, the fatty acids in oil pharmaceutical excipients exist in the free and bound forms, and the low content of free fatty acids in these oil pharmaceutical excipients not only poses challenges for their detection but also complicates the determination of characteristic fatty acid compositions and contents. Moreover, the compositions and ratios of fatty acids are influenced by environmental factors, leading to interconversion between their two forms. In this context, saponification provides a simpler and faster alternative to derivatization. Saponification degrades oils and fats by utilizing the reaction between esters and an alkaline solution, ultimately releasing the corresponding fatty acids. Because this method is more cost effective than derivatization, it is a suitable pretreatment method for the detection of fatty acids in oil pharmaceutical excipients using the SFC-ELSD approach. In this study, we employed SFC-ELSD to simultaneously determine six fatty acids, namely, myristic acid, palmitic acid, stearic acid, arachidic acid, docosanoic acid, and lignoceric acid, in oil pharmaceutical excipients. Saponification of the oil pharmaceutical excipients using sodium hydroxide methanol solution effectively avoided the bias in the determination of fatty acid species and contents caused by the interconversion of fatty acids and esters. The separation of the six fatty acids was achieved within 12 min, with good linearity within their respective mass concentration ranges. The limits of detection and quantification were 5-10 mg/L and 10-25 mg/L, respectively, and the spiked recoveries were 80.93%-111.66%. The method proved to be sensitive, reproducible, and stable, adequately meeting requirements for the analysis of fatty acids in oil pharmaceutical excipients. Finally, the analytical method was successfully applied to the determination of six fatty acids in five types of oil pharmaceutical excipients, namely, corn oil, soybean oil, coconut oil, olive oil, and peanut oil. It can be combined with principal component analysis to accurately differentiate different types of oil pharmaceutical excipients, providing technical support for the rapid identification and quality control of oil pharmaceutical excipients. Thus, the proposed method may potentially be applied to the analysis of complex systems adulterated with oil pharmaceutical excipients.


Assuntos
Cromatografia com Fluido Supercrítico , Excipientes , Ácidos Graxos , Ácidos Graxos/análise , Ácidos Graxos/química , Cromatografia com Fluido Supercrítico/métodos , Excipientes/análise , Excipientes/química , Espalhamento de Radiação , Luz , Óleos/química , Óleos/análise
13.
J Pharm Biomed Anal ; 247: 116256, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38850847

RESUMO

A long-term stability study using high performance liquid chromatography (HPLC) revealed an unidentified impurity in the bromhexine hydrochloride injection, which was employed as a mucolytic agent. Investigations into stress degradation and elemental impurities revealed one of the elemental impurities Fe3+ in this injection as the primary generator of these impurities. This impurity, named N-carboxymethyl bromhexine, was a product formed during drug-excipient interaction between bromhexine and tartaric acid with Fe3+. The structure of the impurity was identified through ultra-high-performance liquid chromatography with diode array detector (UHPLC-DAD), liquid chromatograph mass spectrometer (LC-MS). Further, the formation mechanism of the impurity was discussed. Overall, this study elucidates the cause, origin, and mechanism of an unknown impurity in bromhexine hydrochloride injection, providing a basis for quality control for bromhexine hydrochloride injections and drug products containing both amine and tartaric acid.


Assuntos
Bromoexina , Contaminação de Medicamentos , Excipientes , Bromoexina/química , Bromoexina/análise , Cromatografia Líquida de Alta Pressão/métodos , Excipientes/química , Excipientes/análise , Tartaratos/química , Tartaratos/análise , Espectrometria de Massas/métodos , Estabilidade de Medicamentos , Controle de Qualidade
14.
ScientificWorldJournal ; 2024: 5461358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915814

RESUMO

Pharmaceutical formulations have traditionally relied on plants and their derivatives for various APIs and excipients. In Ghana, the widespread utilization of plantains, irrespective of their ripeness, generates significant waste at every stage of processing, posing disposal issues. Fascinatingly, these wastes, often discarded, possess significant economic potential and can be recycled into valuable raw materials or products. Pectin, a polysaccharide that occurs naturally, has seen a surge in interest in recent times. It has found widespread use in the pharmaceutical sector, particularly as a binding agent in tablet formulations. This study aimed to evaluate pectin from two popular plantain varieties, Apem (M) and Apantu (T) at different ripening stages, for pharmaceutical use as a binding agent in immediate-release tablets. The ripening stages selected were the matured-green (G), half-ripe (H), and full-ripe (R). Acid (D) and alkaline (L) mediums of extraction were employed for each ripening stage for both varieties. Wet granulation method was used to prepare the granules using paracetamol as a model drug, and their flow properties were subsequently assessed. Postcompression tests including, hardness, friability, weight uniformity, disintegration, assay, and in vitro dissolution were also assessed. Granules from all formulation batches had good flow properties indicated by their angle of repose (14.93 ± 1.41-21.80 ± 1.41), Hausner ratio (0.96 ± 0.27-1.22 ± 0.02), and compressibility (%) (7.69 ± 0.002-20.51 ± 0.002). All the tablets passed the uniformity of weight with none deviating by ±5%. The hardness of all the formulated tablets ranged between 3.96 ± 0.32 and 13.21 ± 0.36, while the friability for all tablets was below 1%. The drug content was between 100.1 ± 0.23% and 103.4 ± 0.01%. Tablets formulated with pectin as a binding agent at concentrations of 10% w/v and 15% w/v successfully met the disintegration test criteria for immediate release tablets. However, those prepared with a concentration of 20% w/v (MGL, MHD, MHL, MRD, MRL, TGL, THD, THL, and TRL) did not pass the disintegration test. Consequently, all batches of tablets successfully met the dissolution test requirement (Diss, Q > 75%), except for the batches that did not pass the disintegration test (Diss, Q < 75%). Ultimately, pectins extracted from the peels of Apem and Apantu at different ripening stages using acid and alkaline extraction can be commercially exploited as pharmaceutical binders at varying concentrations in immediate-release tablets.


Assuntos
Pectinas , Comprimidos , Pectinas/química , Gana , Plantago/química , Acetaminofen/química , Excipientes/química
15.
Pharm Res ; 41(6): 1201-1216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834905

RESUMO

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.


Assuntos
Álcoois Benzílicos , Excipientes , Frutose , Transportador de Glucose Tipo 2 , Glucose , Glucosídeos , Goma Arábica , Absorção Intestinal , Lactose , Ratos Sprague-Dawley , Transportador 1 de Glucose-Sódio , Animais , Absorção Intestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Masculino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 2/genética , Ratos , Excipientes/química , Excipientes/farmacologia , Glucose/metabolismo , Lactose/química , Álcoois Benzílicos/farmacologia , Álcoois Benzílicos/farmacocinética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos
16.
AAPS PharmSciTech ; 25(6): 147, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937406

RESUMO

Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid.


Assuntos
Excipientes , Tamanho da Partícula , Excipientes/química , Composição de Medicamentos/métodos , Fosfatos de Cálcio/química , Lactose/química , Química Farmacêutica/métodos , Cátions/química , Praziquantel/química , Magnésio/química
17.
Chem Pharm Bull (Tokyo) ; 72(6): 584-595, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38945947

RESUMO

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.


Assuntos
Comprimidos , Comprimidos/química , Tamanho da Partícula , Composição de Medicamentos , Pós/química , Ácidos Esteáricos/química , Resistência à Tração , Excipientes/química , Solubilidade
18.
Eur J Pharm Biopharm ; 201: 114368, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880401

RESUMO

Continuous manufacturing is gaining increasing interest in the pharmaceutical industry, also requiring real-time and non-destructive quality monitoring. Multiple studies have already addressed the possibility of surrogate in vitro dissolution testing, but the utilization has rarely been demonstrated in real-time. Therefore, in this work, the in-line applicability of an artificial intelligence-based dissolution surrogate model is developed the first time. NIR spectroscopy-based partial least squares regression and artificial neural networks were developed and tested in-line and at-line to assess the blend uniformity and dissolution of encapsulated acetylsalicylic acid (ASA) - microcrystalline cellulose (MCC) powder blends in a continuous blending process. The studied blend is related to a previously published end-to-end manufacturing line, where the varying size of the ASA crystals obtained from a continuous crystallization significantly affected the dissolution of the final product. The in-line monitoring was suitable for detecting the variations in the ASA content and dissolution caused by the feeding of ASA with different particle sizes, and the at-line predictions agreed well with the measured validation dissolution curves (f2 = 80.5). The results were further validated using machine vision-based particle size analysis. Consequently, this work could contribute to the advancement of RTRT in continuous end-to-end processes.


Assuntos
Aspirina , Celulose , Pós , Solubilidade , Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Pós/química , Celulose/química , Aspirina/química , Tamanho da Partícula , Redes Neurais de Computação , Liberação Controlada de Fármacos , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Cristalização , Análise dos Mínimos Quadrados , Excipientes/química
19.
Allergol Immunopathol (Madr) ; 52(3): 60-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721956

RESUMO

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Choque , Humanos , Anafilaxia/diagnóstico , Anafilaxia/terapia , Anafilaxia/etiologia , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/imunologia , Choque/etiologia , Choque/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Masculino , Animais , Imunoglobulina E/imunologia , Excipientes/efeitos adversos , Dissacarídeos/imunologia , Dissacarídeos/efeitos adversos , Feminino , Trissacarídeos/imunologia , Gelatina/efeitos adversos , Síndrome
20.
AAPS PharmSciTech ; 25(5): 107, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730121

RESUMO

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.


Assuntos
Disponibilidade Biológica , Cissus , Sistemas de Liberação de Medicamentos , Emulsões , Osteoporose , Animais , Osteoporose/tratamento farmacológico , Ratos , Cissus/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Administração Oral , Excipientes/química , Solubilidade , Extratos Vegetais/farmacocinética , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Tamanho da Partícula , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...