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1.
Int J Pharm ; : 124722, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39293578

RESUMEN

The manufacturing of pharmaceutical solid dosage forms, such as tablets involves a large number of successive processing operations including crystallisation of the drug substance, granulation, drying, milling, mixing of the formulation, and compaction. Each step is fraught with manufacturing problems. Undesired adhesion of powders to the surface of the compaction tooling, known as sticking, is a frequent and highly disruptive problem that occurs at the very end of the process chain when the tablet is formed. As an alternative to the mechanistic approaches to address sticking, we introduce two different machine learning strategies to predict sticking directly from the chemical formula of the drug substance, represented by molecular descriptors. An empirical database for sticking behaviour was developed and used to train the machine learning (ML) algorithms to predict sticking properties from molecular descriptors. The ML model has successfully classified sticking/non-sticking behaviour of powders with 100% separation. Predictions were made for materials in the handbook of Pharmaceutical Excipients and a subset of molecules included in the ChemBL database, demonstrating the potential use of machine learning approaches to screen for sticking propensity early at drug discovery and development stages. This is the first-time molecular descriptors and machine learning were used to predict and screen for sticking behaviour. The method has potential to transform the development of medicines by providing manufacturability information at drug screening stage and is potentially applicable to other manufacturing problems controlled by the chemistry of the drug substance.

2.
Zhongguo Zhen Jiu ; 44(7): 803-6, 2024 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-38986594

RESUMEN

OBJECTIVE: To observe the clinical efficacy of acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) for postpartum urinary retention. METHODS: A total of 120 patients with postpartum urinary retention were randomly divided a triple-combination group, a double-combination group, and a massage group, with 40 patients in each group. All groups received standard postpartum care to stimulate urination. The patients in the massage group received rapid acupoint massage at the bilateral Shuidao (ST 28); the patients in the double-combination group additionally received acupoint sticking of self-made Tongquan powder at bilateral Shuidao (ST 28); the patients in the triple-combination group further received moxibustion at bilateral Shuidao (ST 28). The treatment was given once in all three groups. After 5 hours of treatment completion, bladder residual volume was measured; the time and volume of first urination as well as total urination volume after 5 hours of treatment completion were recorded; the patients' sensation of urination smoothness, satisfaction rate, length of hospital stay, and hospital costs were evaluated. RESULTS: The triple-combination group showed significantly lower residual urine volumes (P<0.05), earlier first urination time (P<0.05, P<0.001), and higher first urination volumes and total urination volumes after 5 hours of treatment completion compared to the other two groups (P<0.05, P<0.001). The sensation of urination smoothness and patient satisfaction were also significantly better in the triple-combination group (P<0.001, P<0.05). The double-combination group had higher volume of first urination and total urination volume after 5 hours of treatment completion than the massage group (P<0.05), and better sensation of urination smoothness and patient satisfaction (P<0.05). There was no significant difference in the length of hospital stay and costs among the three groups (P>0.05). The total effective rates were 100.0% (40/40) for the triple-combination group, 90.0% (36/40) for the double-combination group, and 70.0% (28/40) for the massage group, with the triple-combination group significantly outperforming the other two groups (P<0.05, P<0.001), and double-combination group outperforming the massage group (P<0.05). CONCLUSION: Acupoint massage, acupoint sticking combined with moxibustion at Shuidao (ST 28) could effectively improve urination in patients with postpartum urinary retention, and enhance patient satisfaction.


Asunto(s)
Puntos de Acupuntura , Masaje , Moxibustión , Periodo Posparto , Retención Urinaria , Humanos , Femenino , Moxibustión/métodos , Retención Urinaria/terapia , Retención Urinaria/fisiopatología , Adulto , Adulto Joven , Terapia Combinada , Resultado del Tratamiento , Micción , Trastornos Puerperales/terapia , Embarazo
3.
Ann Vasc Dis ; 17(2): 164-170, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38919316

RESUMEN

Objectives: To assess the physical features and compression characteristics of a newly developed adjustable compression garment, McBoooon (Mc). Methods: Twelve healthy volunteers were recruited to assess the compression characteristics. The interface pressure (IP) was continuously measured to calculate the static (SSI) and dynamic stiffness indices (DSI). Additionally, the peak flow velocity (PV) of the popliteal vein during ankle dorsiflexion was measured using ultrasonography. Each parameter was compared between ASHIKA stockings (AS), Mc applied at the same resting pressure as AS (Mc1), and Mc applied at a resting pressure approximately twice that of Mc1 (Mc2). Results: SSI and DSI were significantly different, increasing in the order AS < Mc1 < Mc2 (p <0.01). Although the PV was significantly higher in the compression group than in the control group (p <0.05), no significant differences were found among the three groups. Conclusion: The physical features and compression characteristics of Mc were clarified. The high stiffness of this garment improves the adherence to compression therapy and contributes to the treatment of chronic venous insufficiency.

4.
Anim Sci J ; 95(1): e13956, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38797661

RESUMEN

Dry-cured beef ham quality is determined by moisture content; however, it is hard to do non-destructive monitoring. We investigated whether the internal moisture content of dry-cured beef ham could be determined from the impedance of the surface, which is removed at the time of eating. Supraspinatus muscle samples from Japanese Shorthorn steers were dried for different periods. The samples were then divided into the parts to be removed (surface) and edible parts. Their respective impedance and moisture content were measured, and the correlation between these two parameters was investigated. A negative correlation was observed between the impedance and moisture content of the surface and the shallow and deep sections of the edible part. There was also a negative correlation between the impedance of the surface and the moisture content of the shallow and deep sections of the edible part. Therefore, the results of this study indicate that during drying, the moisture content in the shallow and deep sections of dry-cured hams can be estimated by measuring the impedance of the surface. This non-destructive method of measuring the moisture content of dry-cured hams can help in regulating the moisture content during drying to produce high-quality dry-cured hams.


Asunto(s)
Impedancia Eléctrica , Calidad de los Alimentos , Agua , Animales , Agua/análisis , Bovinos , Desecación , Manipulación de Alimentos/métodos , Productos de la Carne/análisis , Análisis de los Alimentos/métodos , Porcinos , Carne Roja/análisis , Masculino , Músculo Esquelético
5.
J Hum Kinet ; 91(Spec Issue): 105-119, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38689586

RESUMEN

This study compared the kinematics, surface electromyography (sEMG) and kinetics among isometric squats performed at 10 different heights of the upward part and a one-repetition maximum (1-RM) squat. Eleven males (age: 27.5 ± 3.4 years, body mass: 84.9 ± 8.1 kg, body height: 1.79 ± 0.06 m, 1-RM squat: 152.2 ± 20.55 kg) took part in this study. It was found that force output was lowest in the sticking region at around the event of peak deceleration for the 1-RM trial with force output at 2179 ± 212 N. For the isometric trial, the lowest force output occurred at the lowest barbell height (1735 ± 299 N). In addition, for the 1-RM condition hip extension moments peaked at the first four barbell heights (6.5-6.2 Nm/kg) representing the pre-sticking and the sticking region before significantly decreasing during the events representing the post-sticking region. Additionally, the sEMG amplitude peaked for the hip extensors at the barbell heights corresponding to the post-sticking region. Moreover, the sEMG amplitude was significantly higher for the 1-RM condition for all hip extensors, vastus lateralis, and calf muscles (F ≥ 2.7, p ≤ 0.01, ηp2 ≥ 0.25). Therefore, we suggest that the sticking region occurs because of reduced force output in the pre-sticking and the sticking region in back squats among resistance-trained males. The reduced force output is probably a combination of suboptimal internal moment arms, length-tension relationships of the gluteus maximus, hamstring and vastii muscles in the pre-sticking and sticking regions to overcome the large extensor moments together with diminishing potentiation from the pre-sticking to the sticking region.

6.
J Funct Morphol Kinesiol ; 9(2)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38651433

RESUMEN

During the ascent phase of a maximal barbell back squat after an initial acceleration, a deceleration region occurs as the result of different biomechanical factors. This is known as the sticking region. However, whether this region is similar in the last repetition of different repetition maximums and if sex has an impact on biomechanics of this region are not known. Therefore, this study investigated the effect of sex (men/women) and repetition maximum (1-, 3-, 6-, and 10RM) on kinematics and surface electromyography around the sticking region. Twenty-six resistance-trained individuals comprising 13 men (body mass: 82.2 ± 8.7; age: 23.6 ± 1.9; height: 181.1 ± 6.5) and 13 women (body mass: 63.6 ± 6.6; age: 23.9 ± 4.5; height: 166.0 ± 4.5) participated in the study. The main findings were that women, in comparison to men, displayed larger trunk lean and lower hip extension angles in the sticking region, possibly due to different hip/knee extensor strength ratios. Moreover, an inverse relationship was discovered between repetition range and timing from V0 to Vmax2, in which lower repetition ranges (1- and 3RM) were shorter in Vmax2 compared to higher ranges (6- and 10RM). It was concluded that this occurrence is due to more moments of inertia in lower repetition ranges. Our findings suggest that both sex and repetition range might induce different requirements during the squat ascent.

7.
Zhongguo Zhen Jiu ; 44(4): 405-410, 2024 Apr 12.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-38621727

RESUMEN

OBJECTIVES: To observe the clinical effect and safety of auricular point sticking combined with periocular needle-embedding therapy for pseudomyopia and prevention of true myopia. METHODS: A total of 269 children with pseudomyopia were randomized into an observation group (134 cases, 2 cases dropped out) and a control group (135 cases, 5 cases dropped out). In the control group, the healthy education was provided. In the observation group, besides the intervention as the control group, the auricular point sticking was delivered at gan (CO12), pi (CO13), xin (CO15) and yan (LO5) on one ear in each treatment, combined with periocular needle-embedding technique at bilateral Cuanzhu (BL 2), Yuyao (EX-HN 4) and Sibai (ST 2). There were 2 weeks of interval after 4 weeks of treatment. One course of treatment was composed of 6 weeks and 2 courses were required. Separately, before treatment, after 6 and 12 weeks of treatment, and after 12 weeks (the 1st follow-up visit) and 24 weeks (the 2nd follow-up visit) of treatment completion, the spherical equivalent (SE), SE progression, axial length (AL) progression, accommodative amplitude (AMP), the score of the TCM symptom and the general symptom were observed in the two groups. The safety and compliance were evaluated in the two groups. RESULTS: After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, SE increased when compared with that before treatment in the two groups (P<0.05), and AMP was larger than that before treatment in the observation group (P<0.05). After 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of SE was slower in the observation group compared with that in the control group (P<0.01, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the progression of AL in the observation group was lower than that of the control group (P<0.05, P<0.01, P<0.001); and in the 1st and 2nd follow-up visits, AMP of the observation group was larger when compared with that in the control group (P<0.05, P<0.001). After 6 and 12 weeks of treatment, and in the 1st and 2nd follow-up visits, the total scores of TCM symptom and general symptom were reduced in comparison with those before treatment in the observation group (P<0.05); after 6 and 12 weeks of treatment, the total scores of TCM symptom and general symptom were lower than those before treatment in the control group (P<0.05). In the 1st and 2nd follow-up visits, the difference of the total score of TCM symptom and general symptom in the observation group was larger than that of the control group (P<0.05). In the observation group, compared with the control group, the scores for pale/dark complexion in the 1st and 2nd follow-up visits and that for lassitude in the 2nd follow-up visit were lower (P<0.05), the score for poor concentration after 12 weeks of treatment and that for poor sleep and memory in the 2nd follow-up visit were lower (P<0.05). There were no adverse reactions in the two groups. The compliance was 98.5% in the observation group and was 96.3% in the control group, without statistical difference (P>0.05). CONCLUSIONS: On the basis of health education, auricular point sticking combined with periocular needle-embedding therapy can effectively prevent from true myopia, control the increase of SE, delay the growth of AL and improve AMP in children with pseudomyopia. This compound therapeutic regimen can relieve the general symptom and comprehensively prevent from myopia through multiple approaches, with high safety and satisfactory compliance.


Asunto(s)
Terapia por Acupuntura , Acupuntura Auricular , Miopía , Niño , Humanos , Acupuntura Auricular/métodos , Puntos de Acupuntura , Miopía/terapia , Terapia por Acupuntura/métodos , Agujas , Resultado del Tratamiento
8.
Cureus ; 16(2): e53461, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38435183

RESUMEN

Introduction The goal of this study was to see how people who had been diagnosed with Mycoplasma pneumoniae pneumonia (MPP) responded to respiratory function training and rehabilitation (RFTR) nursing. Methodology A total of 122 patients (five to 12 years of age) diagnosed with Mycoplasma pneumoniae pneumonia (MPP) and refractory Mycoplasma pneumoniae pneumonia (RMPP) using enzyme-linked immunoassay and PCR were included in this study. These patients were hospitalized at a tertiary care hospital from February 2022 to December 2022. Upon admission, they were assigned a numerical identifier based on the order of admission. Subsequently, they were randomly allocated into two equal groups: the observation (OG) and the control (CG), with each group consisting of 61 patients. Nano-acupoint sticking (NAS) therapy along with respiratory function training and rehabilitation (RFTR) nursing interventions were implemented for patients in the OG. Results The observed disparities in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of FEV1 to FVC among the patients did not exhibit significant disparity prior to the commencement of treatment (p values of 0.700, 0.105, and 0.829, respectively). There was no significant difference observed in the range of inflammation in the right lung (p=0.523). Inflammation in the left lung and fluid volume in both lungs are statistically different in both groups (p values of 0.001 and 0.000, respectively). The patients in the observation group exhibited a shorter duration of cough and sputum, disappearance of lung sounds, and length of hospital stays (LOS) compared to the other groups, with statistical significance (p<0.05). Conclusion Nano-acupoint sticking (NAS) therapy with respiratory function training and rehabilitation (RFTR) in nursing practice has shown enhanced rehabilitation outcomes for individuals diagnosed with Mycoplasma pneumoniae pneumonia (MPP). The present study focuses on the application of NAS therapy in the context of RFTR for individuals diagnosed with MPP.

9.
Int J Pharm ; 652: 123849, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38266938

RESUMEN

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning process was performed using 3.0 kg of Prosolv® and 3.0 kg of Tablettose® 70. The impact of different volumetric feed rates of the cleaning excipient was assessed. The displacement of API and blend residues was evaluated with in-line near infrared (NIR) spectroscopy. Principal component analysis (PCA) was performed to evaluate the cleaning progress as the Prosolv® flowed through the feeder, mixer and stream sampler. In-place Raman spectra were acquired from the material sticking to detect the ibuprofen residues. The study showed that Prosolv® and Tablettose® can remove ibuprofen residues effectively from the hopper, feeder screw, mixer paddles, shaft and stream sampler. The Process Analytical Technology (PAT) system can be utilized to detect API displacement during the cleaning process. However, dismantling and manual cleaning was required to remove material sticking at the surfaces adjacent to the rotating feeder screws and mixer paddles.


Asunto(s)
Química Farmacéutica , Tecnología Farmacéutica , Tecnología Farmacéutica/métodos , Química Farmacéutica/métodos , Excipientes/química , Ibuprofeno/química , Polvos/química , Comprimidos , Composición de Medicamentos/métodos
10.
Int J Pharm ; 653: 123813, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38272192

RESUMEN

Punch sticking during tablet manufacturing is a prevalent issue for many active pharmaceutical ingredients (APIs) encountered by the pharmaceutical industry. Tenofovir amibufenamide fumarate (TMF), a heavyweight drug for the treatment of hepatitis B, was selected as a model drug due to its tendency to punch sticking during tablet compression. In this study, the cause of sticking was explored by investigating crystal habits, excipients and structure characteristics. The difference in sticking of three crystal habits can be visually represented through direct compression experiments on powdered samples and analysis of crystal surfaces. The excipients play a direct role in decreasing the probability of sticking, and the extent of sticking can be assessed by measuring the tensile strength of the tablet. Additionally, the plasticity index was utilized to theoretically analyze the potential enhancements of four excipients. These experimental results indicate that the block-shaped crystals have superior ability of anti-sticking and that suitable excipients can significantly improve the sticking situation of TMF. Ultimately, the phenomenon of punch sticking was additionally examined through computational calculations, focusing on the mechanical characteristics of TMF molecules and intermolecular interactions. The strategy of combining experiments and simulation calculations has broader significance for the study of drug production.


Asunto(s)
Excipientes , Excipientes/química , Comprimidos/química , Presión , Resistencia a la Tracción , Tenofovir , Composición de Medicamentos/métodos
11.
Int J Pharm ; 649: 123636, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38013042

RESUMEN

External lubrication of tooling with magnesium stearate (MgSt) is a common strategy to eliminate punch sticking when compressing powders with a high sticking propensity, such as many pure active pharmaceutical ingredients (APIs). We found that it actually led to aggravated punch sticking at low compaction pressures. This counterintuitive phenomenon was explained based on interplay of forces among the punch tip, MgSt, and API. The explanation is supported by the observed effects of pressure and mechanical properties of APIs on this phenomenon.


Asunto(s)
Ácidos Esteáricos , Composición de Medicamentos , Comprimidos , Lubrificación
12.
Heliyon ; 9(12): e22366, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38076043

RESUMEN

Pipe sticking is a major problem that can result in significant downtime, lost productivity, and increased costs. The aim of this study is to develop an accurate and effective predictive model for pipe sticking due to wellbore uncleanliness using a range of classification algorithms. In this research work, the drilling data from two different reservoirs in India was pre-processed and eviscerated to ensure that it was suitable to process using classification algorithms. The data collected from two different reservoirs in India were analyzed using different machine learning algorithms to tackle the persistent challenges of pipe sticking during oil drilling operations. These algorithms were compared and evaluated based on their performance. The research finding indicates that the ensemble classifier algorithm performs better than a single classifier algorithm. It shows high generalization ability with an average accuracy of around 90 %. In addition to this, the ensemble classifier algorithm possesses good classification performance, and provides immunity from noisy data, offering strong support for real-time detection to prevent pipe sticking thereby reducing costly downtime.

13.
AAPS PharmSciTech ; 24(8): 237, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37989970

RESUMEN

"Sticking" during tablet manufacture is the term used to describe the accumulation of adhered tablet material on the punch over the course of several compaction cycles. The occurrence of sticking can affect tablet weight, image, and structural integrity and halt manufacturing operations. The earlier the risk of sticking is detected during R&D, the more options are available for mitigation and the less potential there is for significant delays and costs. The detection osf sticking, however, during the early stages of drug development is challenging due to the limitations of available material quantity. In this work, single tablet multi-compaction (STMC) and a highly sensitive laser reflection sensor are used to detect the propensity of sticking with ibuprofen powder blends. STMC can differentiate the various formulations and replicates the trends of sticking at different punch speeds. The results demonstrate the potential for STMC to be used as an extremely material sparing (requiring very few tablets) methodology for the assessment of sticking during early-stage development.


Asunto(s)
Ibuprofeno , Adhesividad , Composición de Medicamentos/métodos , Comprimidos/química , Ibuprofeno/química , Polvos/química
14.
Molecules ; 28(22)2023 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-38005267

RESUMEN

The adsorption of nitrogen molecules on a (100) tungsten surface has been studied using a new potential energy surface in which long-range interactions are suitably characterized and represented by the Improved Lennard-Jones function. The new potential energy surface is used to carry out molecular dynamics simulations by adopting a semiclassical collisional method that explicitly includes the interaction with the surface phonons. The results of the sticking probability, evaluated as a function of the collision energy, are in good agreement with those obtained in the experiments and improve the already good comparison recently obtained with calculations performed using interactions from the Density Functional Theory method and corrected for long-range van der Waals contributions. The dependence of trapping probability on the surface temperature for a well-defined collision energy has also been investigated.

15.
Pharm Dev Technol ; 28(10): 992-999, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37938090

RESUMEN

Punch sticking is a recurrent problem during the pharmaceutical tableting process. Powder moisture content plays a key role in the buildup of sticking; it evaporates due to increased tablet temperature, accumulates at the punch-tablet interface, and causes sticking through capillary force. This study investigated the effects of compaction pressure (CP), compaction speed (CS), and lubrication level (magnesium stearate (MgSt) ratio) on tablet surface temperature (TST) and tablet surface moisture content (TSMC). TST and TSMC were measured with an infrared thermal camera and near-infrared sensor, respectively. Microcrystalline cellulose was used as the tableting powder and MgSt as the lubricant. The low range of CS values (16-32 mm/s) considered in this study did not have significant effects on TST and TSMC. MgSt ratio had a significant positive effect on TST; this may be explained by the increase in powder blend effusivity with the addition of MgSt. However, MgSt ratio did not have a significant effect on TSMC. CP had a significant positive effect on both TST and TSMC. Increased CP induced higher heat generation through particle deformation and friction during the compaction phase, leading to increased TST. Furthermore, the water vapor diffusion rate through the powder bed might have increased due to the rise in thermal energy and led to further moisture accumulation at the tablet-punch interface, causing the significant positive effect of CP on TSMC. This result may explain the occurrence of sticking regardless of the CP applied during the tableting process.


Asunto(s)
Lubricantes , Ácidos Esteáricos , Lubrificación , Polvos/química , Temperatura , Lubricantes/química , Comprimidos/química , Ácidos Esteáricos/química
16.
AAPS PharmSciTech ; 24(7): 209, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37817056

RESUMEN

Sticking to tablet punches is a major issue during drug product manufacturing. Research has shown that sticking involves the interrelationship of powder properties, compression force, length of manufacturing runs and punch quality. Here, we present a novel non-destructive methodology to study the surface metrology of punches to monitor them over their lifetime. This investigation used a non-contact laser interferometer to characterise roughness of commercial standard S7 steel punches coated with chrome that were originally used for commercial scale production that developed a sticking issue. During the development, this phenomenon had not been observed and was not considered a scale-up risk. The profilometer was used to examine the complete surface of these punches to investigate whether they met the acceptability criteria based on BS_ISO_18804 tooling standard. To improve data analysis during changeover, a 3D-printed holder was designed to enable analysis with minimal set-up requirements. Upon investigation, the punches were found to be of an unacceptable roughness and, particularly rough areas of the punch surface profiled, correlated well with areas of visually pronounced sticking. This non-destructive method can be used to produce a more detailed characterisation of punch roughness to ensure surfaces are of an acceptable quality after treatment with coatings.


Asunto(s)
Fenómenos Mecánicos , Adhesividad , Comprimidos , Presión , Propiedades de Superficie , Composición de Medicamentos/métodos
17.
Zhongguo Zhen Jiu ; 43(7): 776-80, 2023 Jul 12.
Artículo en Chino | MEDLINE | ID: mdl-37429657

RESUMEN

OBJECTIVE: To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP). METHODS: Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated. RESULTS: Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions. CONCLUSION: Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.


Asunto(s)
Terapia por Acupuntura , Pubertad Precoz , Femenino , Humanos , Pubertad Precoz/terapia , Estradiol , Hormona Luteinizante , Ovario
18.
Pharmaceutics ; 15(6)2023 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-37376100

RESUMEN

The moisture content of pharmaceutical powder is a key parameter contributing to tablet sticking during the tableting process. This study investigates powder moisture behavior during the compaction phase of the tableting process. Finite element analysis software COMSOL Multiphysics® 5.6 was used to simulate the compaction microcrystalline cellulose (VIVAPUR PH101) powder and predict temperature and moisture content distributions, as well as their evolution over time, during a single compaction. To validate the simulation, a near-infrared sensor and a thermal infrared camera were used to measure tablet surface temperature and surface moisture, respectively, just after ejection. The partial least squares regression (PLS) method was used to predict the surface moisture content of the ejected tablet. Thermal infrared camera images of the ejected tablet showed powder bed temperature increasing during compaction and a gradual rise in tablet temperature along with tableting runs. Simulation results showed that moisture evaporate from the compacted powder bed to the surrounding environment. The predicted surface moisture content of ejected tablets after compaction was higher compared to that of loose powder and decreased gradually as tableting runs increased. These observations suggest that the moisture evaporating from the powder bed accumulates at the interface between the punch and tablet surface. Evaporated water molecules can be physiosorbed on the punch surface and cause a capillary condensation locally at the punch and tablet interface during dwell time. Locally formed capillary bridge may induce a capillary force between tablet surface particles and the punch surface and cause the sticking.

19.
Int J Pharm ; 641: 123041, 2023 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-37201765

RESUMEN

The development of a high quality tablet of Celecoxib (CEL) is challenged by poor dissolution, poor flowability, and high punch sticking propensity of CEL. In this work, we demonstrate a particle engineering approach, by loading a solution of CEL in an organic solvent into a mesoporous carrier to form a coprocessed composite, to enable the development of tablet formulations up to 40% (w/w) of CEL loading with excellent flowability and tabletability, negligible punch sticking propensity, and a 3-fold increase in in vitro dissolution compared to a standard formulation of crystalline CEL. CEL is amorphous in the drug-carrier composite and remained physically stable after 6 months under accelerated stability conditions when the CEL loading in the composite was ≤ 20% (w/w). However, crystallization of CEL to different extents from the composites was observed under the same stability condition when CEL loading was 30-50% (w/w). The success with CEL encourages broader exploration of this particle engineering approach in enabling direct compression tablet formulations for other challenging active pharmaceutical ingredients.


Asunto(s)
Portadores de Fármacos , Excipientes , Celecoxib , Composición de Medicamentos , Solubilidad , Comprimidos/química , Portadores de Fármacos/química , Excipientes/química
20.
Int J Pharm ; 640: 123016, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37156307

RESUMEN

The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.


Asunto(s)
Ácidos Esteáricos , Composición de Medicamentos/métodos , Presión , Fenómenos Físicos , Comprimidos
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