| 1. |
- Brülls, Mikael, et al.
(författare)
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Applying spectral peak area analysis in near-infrared spectroscopy moisture assays
- 2007
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Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085. ; 44:1, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- Spectral peak area analysis has in this study been shown to be a viable method in near-infrared spectroscopy (NIRS) moisture assays. The study also shows that the required number of calibration samples can be minimized, and the method is, therefore, especially suitable for moisture assays in early formulation development and in-situ process monitoring.Diffuse NIRS was utilized in the development of moisture assays for the model compounds polyvinylpyrrolidone and hydroxypropyl-beta-cyclodextrin and also for a lyophilized formulation. Reference data were obtained using coulometric Karl Fischer titration. The NIRS measurements were performed through the bottoms of the sample vials using either a Fourier Transform-Near-infrared (FT-NIR) spectrometer fitted with a diffuse reflectance probe or a dispersive single beam spectrometer. The ratios of the peak areas of a water peak at 5200 cm(-1) and a reference peak were evaluated using linear regression analysis. The spectral peak area analysis method was compared with a conventional partial least squares regression method. The moisture assays were verified using independent test sets. The investigated moisture range was 0-22% for the samples of PVP, 0-8.5% for the samples of hydroxypropyl-beta-cyclodextrin and 0.5-8.5% for the samples of the lyophilized formulation.The results of the spectral peak area analysis and the conventional partial least squares regression were similar, but the peak area method was more robust and could also make accurate predictions for lyophilized PVP samples, although the calibration set consisted of non-lyophilized samples. The peak area method required fewer calibration samples than the conventional partial least squares regression method.
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| 2. |
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| 3. |
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| 4. |
- Bonmann, Marlene, 1988, et al.
(författare)
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Terahertz radar observes powder dynamics for pharmaceutical manufacturing
- 2024
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Ingår i: IEEE Sensors Journal. - 1558-1748 .- 1530-437X. ; 24:13, s. 20512-20522
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Tidskriftsartikel (refereegranskat)abstract
- The optical opaqueness of powders has precluded the observation of powder flow dynamics in processing tubes, with important implications, for example, in the pharmaceutical industry, where non-destructive monitoring during the manufacturing process is essential to ensure the quality of the final product and the effectiveness of the process. Taking advantage of the high penetration of terahertz electromagnetic waves in powders and its wavelength-to-particle size ratio, we demonstrate that a submillimeter-wave pulse-Doppler radar can overcome the present challenges and characterize powder flow dynamics in pharmaceutical manufacturing processes. Mimicking typical vessel shapes in pharmaceutical operations, we were able to characterize falling powder streams in a tube with a sample volume resolution of a few cubic centimeters and a range resolution of about 5 mm. We successfully monitored particle velocity, particle distribution within the tube, and mass flow rate in real-time. This remote sensing method, based on advanced terahertz electronics, opens up the possibility to study and monitor powder dynamics in a wide range of applications.
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| 5. |
- Carlander, Christina, et al.
(författare)
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HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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| 6. |
- Carlander, Christina, et al.
(författare)
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Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia
- 2018
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Ingår i: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 32:11, s. 1475-1484
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.
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| 7. |
- Dumarey, Melanie, 1982-, et al.
(författare)
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Combining experimental design and orthogonal projections to latent structures to study the influence of microcrystalline cellulose properties on roll compaction
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 416:1, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Roll compaction is gaining importance in pharmaceutical industry for the dry granulation of heat or moisture sensitive powder blends with poor flowing properties prior to tabletting. We studied the influence of microcrystalline cellulose (MCC) properties on the roll compaction process and the consecutive steps in tablet manufacturing. Four dissimilar MCC grades, selected by subjecting their physical characteristics to principal components analysis, and three speed ratios, i.e. the ratio of the feed screw speed and the roll speed of the roll compactor, were included in a full factorial design. Orthogonal projection to latent structures was then used to model the properties of the resulting roll compacted products (ribbons, granules and tablets) as a function of the physical MCC properties and the speed ratio. This modified version of partial least squares regression separates variation in the design correlated to the considered response from the variation orthogonal to that response. The contributions of the MCC properties and the speed ratio to the predictive and orthogonal components of the models were used to evaluate the effect of the design variation. The models indicated that several MCC properties, e.g. bulk density and compressibility, affected all granule and tablet properties, but only one studied ribbon property: porosity. After roll compaction, Ceolus KG 1000 resulted in tablets with obvious higher tensile strength and lower disintegration time compared to the other MCC grades. This study confirmed that the particle size increase caused by roll compaction is highly responsible for the tensile strength decrease of the tablets.
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| 8. |
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| 9. |
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| 10. |
- Kamran, Faisal, et al.
(författare)
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Transmission Near-Infrared (NIR) and Photon Time-of-Flight (PTOF) Spectroscopy in a Comparative Analysis of Pharmaceuticals
- 2015
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Ingår i: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 69:3, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive study of the application of photon time-of-flight spectroscopy (PTOFS) in the wavelength range 1050 1350 nm as a spectroscopic technique for the evaluation of the chemical composition and structural properties of pharmaceutical tablets. PTOFS is compared to transmission near-infrared spectroscopy (NIRS). In contrast to transmission NIRS, PTOFS is capable of directly and independently determining the absorption and reduced scattering coefficients of the medium. Chemometric models were built on the evaluated absorption spectra for predicting tablet drug concentration. Results are compared to corresponding predictions built on transmission NIRS measurements. The predictive ability of PTOFS and transmission NIRS is comparable when models are based on uniformly distributed tablet sets. For non-uniform distribution of tablets based on particle sizes, the prediction ability of PTOFS is better than that of transmission NIRS. Analysis of reduced scattering spectra shows that PTOFS is able to characterize tablet microstructure and manufacturing process parameters. In contrast to the chemometric pseudovariables provided by transmission NIRS, PTOFS provides physically meaningful quantities such as scattering strength and slope of particle size. The ability of PTOFS to quantify the reduced scattering spectra, together with its robustness in predicting drug content, makes it suitable for such evaluations in the pharmaceutical industry.
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| 11. |
- Khoptyar, Dmitry, et al.
(författare)
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Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly scattering plastics in the VIS and close NIR spectral ranges
- 2013
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Ingår i: Optics Express. - 1094-4087. ; 21:18, s. 20941-20953
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Tidskriftsartikel (refereegranskat)abstract
- We present extended spectroscopic analysis of pharmaceutical tablets in the close near infrared spectral range performed using broadband photon time-of-flight (PTOF) absorption and scattering spectra measurements. We show that the absorption spectra can be used to perform evaluation of the chemical composition of pharmaceutical tablets without need for chemo-metric calibration. The spectroscopic analysis was performed using an advanced PTOF spectrometer operating in the 650 to 1400 nm spectral range. By employing temporal stabilization of the system we achieve the high precision of 0.5% required to evaluate the concentration of tablet ingredients. In order to further illustrate the performance of the system, we present the first ever reported broadband evaluation of absorption and scattering spectra from pure and doped Spectralon (R). (C) 2013 Optical Society of America
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| 12. |
- Knight, Ann, et al.
(författare)
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Urinary bladder cancer in Wegener's granulomatosis : risks and relation to cyclophosphamide
- 2004
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 63:10, s. 1307-1311
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis.METHODS:In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated.RESULTS:The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis.CONCLUSION:The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.
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| 13. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Monitoring the Porosity of Pharmaceutical Tablets Using THz Frequency Domain Spectroscopy
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, terahertz frequency domain spectroscopy (THz-FDS) in transmission mode has been employed to study the impact of design parameters of tablets such as initial particle size, drug concentration and compaction force, on their porosity. The complex transmission coefficient S21 of 69 tablets were measured using a vector network analyzer in the frequency range of 500-750 GHz. The results show that excipient particle size and compaction force have significant effects on the pore structure of the tablets and THz-FDS reveals to be a very promising tool in monitoring the porosity of pharmaceutical tablets.
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| 14. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Small Variation of Active Pharmaceutical Ingredient Concentration Can Be Observed with THz Frequency Domain Spectroscopy
- 2021
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035. ; 2021-August
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Konferensbidrag (refereegranskat)abstract
- Terahertz frequency-domain spectroscopy (THz-FDS) has been employed to study the result of the variation of active pharmaceutical ingredients (API) on the effective refractive index of pharmaceutical tablets. A quasi-optical set-up with four off-axis parabolic mirrors was used to measure the effective refractive index of tablets in the frequency range of 500-750 GHz. It was observed that a small variation in API concentration can be detected using accurate measurements of the complex transmission coefficients. As a result, THz-FDS reveals to be an effective technique in monitoring the physical properties of pharmaceutical tablets
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| 15. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz Frequency-Domain Sensing Combined with Quantitative Multivariate Analysis for Pharmaceutical Tablet Inspection
- 2023
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination (?2) for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6% for tablet density and API concentration models, respectively. In conclusion, terahertz spectroscopy demonstrated to be a complementary technique to Raman and NIR spectroscopy, which enables the characterization of physical properties of tablets like tablet density, and the characterization of API concentration with the advantage of low scattering effects.
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| 16. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 618
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Tidskriftsartikel (refereegranskat)abstract
- Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in-situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500-750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behavior of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in-situ sensing in tablet manufacturing.
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| 17. |
- Moradikouchi, Anis, 1990, et al.
(författare)
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Terahertz radar sensing for real-time monitoring of powder streams
- 2023
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Ingår i: International Conference on Infrared, Millimeter, and Terahertz Waves, IRMMW-THz. - 2162-2027 .- 2162-2035.
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Konferensbidrag (refereegranskat)abstract
- In pharmaceutical manufacturing processes, the flow properties of powder streams moving in the manufacturing pipes directly impact the properties of the final drug product, and there is a need for real-time non-invasive monitoring of the powder flow properties with process analytical tools. In this study, we propose a frequency-modulated continuous wave (FMCW) Doppler radar system with a center frequency of 340 GHz to measure the flow properties of falling powder streams in a vertical transparent tube. We successfully measured the velocity profile and powder flow density variation along the height of the tube with a spatial resolution of about 5 mm. In conclusion, the terahertz FMCW Doppler radar system was shown to be highly promising for real-time sensing of flow properties of powder streams in the pharmaceutical manufacturing processes.
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| 18. |
- Näsman, Anders, et al.
(författare)
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Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden : an epidemic of viral-induced carcinoma?
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 362-6
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Tidskriftsartikel (refereegranskat)abstract
- In the county of Stockholm, between 1970 and 2002, we have previously reported a 3-fold parallel increase in the incidence of tonsillar squamous cell carcinoma (SCC) and the proportion of human papillomavirus (HPV) positive tonsillar SCC. Here, we have followed the above parameters in all patients (n = 120) diagnosed with tonsillar SCC during 2003-2007 in the same area, and also in correlation to our previous data. Ninety-eight pretreatment biopsies were available and presence of HPV DNA and HPV-16 E6 and E7 RNA were tested by polymerase chain reaction (PCR) and RT-PCR. Incidence data were obtained from the Swedish Cancer Registry. Data reported from 1970 to 2002 were also obtained for comparison. HPV DNA was present in 83 of 98 (85%) of the tonsillar SCC biopsies from 2003 to 2007 and 77 of these were HPV-16 positive. HPV-16 E6 and E7 RNA were found in 98% of 52 analyzed HPV-16 positive cases. The proportion of HPV-positive cancers had significantly increased both from 1970 to 2007 (p < 0.0001) as well from 2000 to 2007 (p < 0.01), with 68% (95% confidence interval (CI), 53-81) 2000-2002; 77% (95% CI, 63-87) 2003-2005; and 93% (95% CI, 82-99) 2006-2007. The incidence rate of HPV-positive tumors almost doubled each decade between 1970 and 2007, in parallel with a decline of HPV-negative tumors. In conclusion, the incidence of HPV-positive cancers is still increasing in the County of Stockholm, suggesting an epidemic of a virus-induced carcinoma, with soon practically all tonsillar SCC being HPV positive, as in cervical cancer.
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| 19. |
- Rehn, Moa, et al.
(författare)
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Highest Vaccine Uptake after School-Based Delivery - A County-Level Evaluation of the Implementation Strategies for HPV Catch-Up Vaccination in Sweden
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background The Swedish school-based vaccination programme offers HPV vaccine to girls born >= 1999 in 5-6th grade. In 2012, all counties introduced free-of-charge catch-up vaccination campaigns targeting girls born 1993-1998. Varying vaccine uptake in the catch-up group by December 2012 suggested that some implementation strategies were more successful than others. In order to inform future vaccination campaigns, we assessed the impact of different implementation strategies on the county-level catch-up vaccine uptake. Methods We conducted an ecological study including all Swedish counties (n = 21), asking regional health offices about the information channels they used and where vaccination of the catch-up target group took place in their counties. The uptake of >= 1 dose by 30 September 2014 was estimated using data from the voluntary national vaccination register. We investigated associations between counties' catch-up vaccine uptake, information channels and vaccination settings by calculating incidence rate ratios (IRR) and 95% confidence intervals (CI), using negative binomial regression models. Results County level catch-up vaccine uptake varied between 49-84%. All counties offered vaccination through primary health care settings. Apart from this eight (34%) also offered the vaccine in some of their schools, four (19%) in all their schools, and two (10%) in other health care centres. The information channels most frequently used were: information at the national on-line health care consulting web-page (100%), letter/invitations (90%), and advertisement (81%). Counties offering vaccination to girls in all schools and counties offering vaccination in some of their schools, reached higher vaccine uptake compared to counties not offering vaccination in any of their schools (all schools adjusted IRR: 1.3, 95% CI: 1.1-1.5, some schools adjusted IRR: 1.2, 95% CI: 1.1-1.3). Conclusion Counties offering HPV vaccination to catch-up groups in schools reached the highest vaccine uptake. No information channel explained differences in county-level vaccine uptake. Our findings suggest that catch-up vaccination outside the national vaccination program can reach a high uptake at the population level if it is implemented primarily with an organized delivery (e.g. in schools).
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| 20. |
- Sundström, Karin, et al.
(författare)
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Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix.
- 2010
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755 .- 1055-9965. ; 19:10, s. 2469-78
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Tidskriftsartikel (refereegranskat)abstract
- The link between squamous cell cervical carcinoma and human papillomavirus (HPV) 16/18 is well established, but the magnitude of the risk association is uncertain and the importance of other high-risk HPV (HRHPV) types is unclear.
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