Optimizing Tabletting Processes with Quality by Design: An Overview

he elements of quality by design are examined and a consistent nomenclature for quality by design, critical quality attribute, critical process parameter, critical material attribute, and control strategy is proposed. A process is well understood when all critical sources of variability are identified and explained, variability is managed by the process, and product quality attributes can be accurately and reliably predicted over the design space. Quality by Design (QbD) is a systematic approach to development of products and processes that begins with predefined objectives and emphasizes product and process understanding and process control based on sound science, statistical methods and quality risk management. In an attempt to curb rising development costs and regulatory barriers to innovation and creativity, the FDA and ICH have recently started promoting QbD in the pharmaceutical industry [1, 3, 7,]. QbD is partially based on the application of multivariate statistical methods [2, 4, 6] and a statistical Design of Experiments strategy [4, 5, 6] to the development of both analytical methods and pharmaceutical formulations. The talk will review the basics of QbD with case studies from the pharmaceutical industr

'If I cannot access services then there is no reason for me to test': the impact of health service charges on HIV testing and treatment amongst migrants in England

Policy governing entitlement to access government health care for foreign nationals in England is a subject of debate, controversy and confusion. Of particular concern to health providers has been the impact of National Health Service charges on delaying HIV testing and anti-retroviral treatment uptake and adherence amongst certain migrant groups. Data obtained through focus groups with 70 migrants from southern Africa, suggest that confusion over health care entitlements exists amongst those seeking health care and is reported amongst health service providers. This confusion, as well as financial difficulties and fears over deportation facing some migrants, can in turn be a factor influencing their decisions to avoid formal health services, resort to alternative and often ineffective or potentially adverse forms of therapy, and delay HIV testing and treatment uptake

Damping Rotor Nutation Oscillations in a Gyroscope with Magnetic Suspension

A possibility of an effective damping of rotor nutations by modulating the field of the moment transducers in synchronism with the nutation frequency is considered. The algorithms for forming the control moments are proposed and their application is discussed

Excitations in opal photonic crystals infiltrated with polarizable media

Journal ArticlePhotonic crystals (PC) are a class of artificial structures with a periodic dielectric function. PCs can be a laboratory for testing fundamental processes involving interactions of radiation with matter in novel conditions. We have studied the optical properties of opal PCs that are infiltrated with highly polarizable media such as J-aggregates of cyanine dyes. Opals are self-assembled structures of silica (Si02) spheres. We report our studies on clarifying the relationship between a polaritonic gap and a photonic stop band (Bragg gap) when they resonantly coexist in the same structure. Infiltration of opal with polarizable molecules combines the polaritonic and Bragg diffractive effects. Both effects exist independently when the Bragg (at ω = ωB) and polaritonic (at ω = ωT) resonances are well separated in frequency. A completely different situation occurs when ωT ~ ωB- Such a condition was achieved in opals that were infiltrated with J-aggregates of cyanine dyes that have large Rabi frequency. Our measurements show some dramatic changes in the shape of the reflectivity plateaus, which are due to the interplay between the photonic band gap and the polaritonic gap. The experimental results on reflectivity and its dependence on the light propagation angle and concentration of the cyanine dyes are in agreement with the theoretical calculations

Excitation energy dependence of photoinduced absorption in intrinsic a-Si:H

Journal ArticleWe have studied subgap absorption of intrinsic a-Si:H induced by below- and above-gap photoexcitation. We find very similar photoinduced subgap absorption spectra when excited with 2.4 eV or 1.2 eV light. Both spectra exhibit a power-law dependence on laser intensity ?T ~ 1a, where a is 0.5 and 0.7 for 2.4 and 1.2 eV excitation energy, respectively. This behavior indicates a change in the recombination mechanism as a function of excitation energy. The PA spectrum excited at 1.2 eV shows a strong dependence on bias illumination. Bias illumination bleaches the absorption according to a power-law as ?T = c(Ebias)-I(1, where P is approximately 0.85 and independent of probe energy and bias energy. The parameter c(Ebias) increases superlinearly with bias illumination energy for Ebias > 1.7 e

Optically detected magnetic resonance studies of undoped a-Si:H

Journal ArticlePhotogenerated carrier dynamics in undoped a-Si:H have been studied by photoinduced absorption (PA), photoluminescence (PL) and their respective optically detected magnetic resonances: PADMR and PLDMR. We have detected for the first time the "g = 4" resonance in PADMR in addition to the previously measured narrow and broad resonances at g ≈ 2. We compare the PADMR and PLDMR resonances over a broad spectral range of detection energies and conclude from the similarities that they share a common underlying mechanism. The PADMR spectra of the narrow and the broad resonances at g ≈ 2 , measured in the spectral range of 0.7 to 1.7 eV, suggest that a correlation exists between the two resonances and PA

Spin dependent photoinduced absorption in a-Si:H

Journal ArticleWe have studied photoexcitation dynamics in undoped a-Si:H from 80 K to 300 K by the techniques of photoluminescence (PL), photoinduced absorption (PA) and their respective versions of optically detected magnetic resonance, namely PLDMR and PADMR. Both PL and PA spectra are composed of low and high energy bands, respectively. Using their respective temperature dependences we correlate the low energy PA band (~0.4 eV) to the high energy PL band (~1.3 eV) and the high energy PA band (~ 1 eV) to the low energy PL band (~0.8 eV). We also found that the PADMR spectrum is composed of three main contributions: a narrow resonance at g ~ 2 (FWHM = 15 G), a broad resonance at g ~ 2 (160 G) and a narrow asymmetric resonance at g ~ 4 (20 G). By measuring their photon energy spectrum we found that the g ~ 4 and the broad g ~ 2 resonances are correlated with each other and therefore are due to trapped electron-hole pairs in the triplet spin configuration

The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

BACKGROUND: Nuclear factor kappa B (NFκB) is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs). Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA) and the pan-RAR antagonist, AGN193109. RESULTS: At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9) and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1), in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. CONCLUSION: We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids

Amplified resonant Raman scattering in conducting polymer thin films

Journal ArticleUsing picosecond pulsed laser excitation, we investigate the optical emission characteristics of poly(2,5-dioctyloxy-p-phenylenevinylene), (DOO-PPV), thin films at high excitation intensities (~1-90 MW/cm2). We observe the presence of amplified resonance Raman scattering in the emission spectra of conducting polymer films. The effect results in sharp Raman lines (widths smaller than 3 Å) superimposed on a significantly broader, well known, spectrally narrowed emission band (width ~10 nm) caused by the amplified spontaneous emission in the waveguided polymer film. At the highest used excitation intensities, Raman scattering dominates the DOO-PPV emission spectrum resulting in a highly monochromatic, single-line emission spectrum

Raman scattering gain in DOO-PPV films

Journal ArticleWe have investigated the optical emission characteristics of poly(2,5-dioctyloxy-p-phenylenevinylene) (DOO-PPV) thin films under high intensity ps pulsed laser excitation (Ipump > 1 MW/ cm2). We observed that the emission spectrum consist of a spectrally narrowed emission (SNE) band (FWHM ~ 10 nm) and superimposed sharp spectral lines. High resolution spectral measurements conducted at room and liquid nitrogen temperatures show that the spectral width of these lines is less than 1 nm. The lines peak positions are independent of film thickness, however, they shifts upon changing the excitation wavelength. Also, the excitation intensity dependence of these narrow lines is found to be different from that of the SNE band. We argue that the narrow lines are due to Raman scattering gain of the 1st, 2nd and 3d order Raman active modes of DOO-PPV