Combining diagnostic methods for antimicrobial susceptibility testing - A comparative approach.

BACKGROUND: The minimum inhibitory concentration (MIC) is a measure of antimicrobial susceptibility testing (AST) of a given antibiotic but provides insufficient information when bacterial killing is crucial, e.g., when treating immunocompromised patients. In these cases, the minimum bactericidal concentration (MBC) is a more reliable measure of antibiotic activity. Here, we aim to demonstrate and recommend combinations of methods for MIC and MBC measurements. We also aim to emphasize the importance of uniform protocols for these procedures including the time point for reading MIC results, which the authors suggest to be 20h. METHODS: To address the challenges with obtaining fast and reliable readouts on MIC as well as the kinetic and end-point effects of antibiotics, the broth micro dilution method, a calorimetric method and a microscopy-based screening system (MBSS) were evaluated in this study. For MBC determination, fluorophore staining with SYTO9 and propidium iodide was compared to the broth regrowth method. RESULTS: Three scenarios for combining the MIC and MBC methods depending on the investigators' primary concern (time, cost or sensitivity) are presented. Further, as the MBSS and the isothermal microcalorimetry method detected delayed bacterial growth up to 18h after initiation of experiments, the importance of reading MIC testing after a full 20h is emphasized. A one-fold change in MIC values can be observed when comparing data obtained at 16h and 20h of incubation. CONCLUSION: The authors suggest that combining MIC and MBC determinations will provide more detailed understanding of the bacteria susceptibility to antibiotic drugs and result in more clinically relevant data and optimized therapies. Furthermore, establishing 20h as a time point for reading MIC results will provide more uniform data across laboratories.

Rapid Assessment of Tablet Film Coating Quality by Multispectral UV Imaging.

Chemical imaging techniques are beneficial for control of tablet coating layer quality as they provide spectral and spatial information and allow characterization of various types of coating defects. The purpose of this study was to assess the applicability of multispectral UV imaging for assessment of the coating layer quality of tablets. UV images were used to detect, characterize, and localize coating layer defects such as chipped parts, inhomogeneities, and cracks, as well as to evaluate the coating surface texture. Acetylsalicylic acid tablets were prepared on a rotary tablet press and coated with a polyvinyl alcohol-polyethylene glycol graft copolymer using a pan coater. It was demonstrated that the coating intactness can be assessed accurately and fast by UV imaging. The different types of coating defects could be differentiated and localized based on multivariate image analysis and Soft Independent Modeling by Class Analogy applied to the UV images. Tablets with inhomogeneous texture of the coating could be identified and distinguished from those with a homogeneous surface texture. Consequently, UV imaging was shown to be well-suited for monitoring of the tablet coating layer quality. UV imaging is a promising technique for fast quality control of the tablet coating because of the high data acquisition speed and its nondestructive analytical nature.

Multispectral UV imaging for fast and non-destructive quality control of chemical and physical tablet attributes.

Monitoring of tablet quality attributes in direct vicinity of the production process requires analytical techniques that allow fast, non-destructive, and accurate tablet characterization. The overall objective of this study was to investigate the applicability of multispectral UV imaging as a reliable, rapid technique for estimation of the tablet API content and tablet hardness, as well as determination of tablet intactness and the tablet surface density profile. One of the aims was to establish an image analysis approach based on multivariate image analysis and pattern recognition to evaluate the potential of UV imaging for automatized quality control of tablets with respect to their intactness and surface density profile. Various tablets of different composition and different quality regarding their API content, radial tensile strength, intactness, and surface density profile were prepared using an eccentric as well as a rotary tablet press at compression pressures from 20MPa up to 410MPa. It was found, that UV imaging can provide both, relevant information on chemical and physical tablet attributes. The tablet API content and radial tensile strength could be estimated by UV imaging combined with partial least squares analysis. Furthermore, an image analysis routine was developed and successfully applied to the UV images that provided qualitative information on physical tablet surface properties such as intactness and surface density profiles, as well as quantitative information on variations in the surface density. In conclusion, this study demonstrates that UV imaging combined with image analysis is an effective and non-destructive method to determine chemical and physical quality attributes of tablets and is a promising approach for (near) real-time monitoring of the tablet compaction process and formulation optimization purposes.

Quality of generic medicines in South Africa: perceptions versus reality - a qualitative study.

BACKGROUND: Generic Medicines are an important policy option allowing for access to affordable, essential medicines. Quality of generic medicines must be guaranteed through the activities of national medicines regulatory authorities. Existing negative perceptions surrounding the quality of generic medicines must be addressed to ensure that people use them with confidence. Campaigns to increase the uptake of generic medicines by consumers and providers of healthcare need to be informed by local norms and practices. This study sought to compare South African consumers' and healthcare providers' perceptions of quality of generics to the actual quality of selected products. METHODS: The study was conducted at the local level in three cities of South Africa: Johannesburg, Durban and Cape Town. Purposive sampling was used to recruit consumer participants (n = 73) and random sampling used to recruit healthcare providers from public and private sectors (n = 15). Data were obtained through twelve focus group discussions with consumers and semi-structured interviews (n = 15) with healthcare providers in order to gain familiarity with perceptions of quality. One hundred and thirty five products comprising paracetamol tablets (n = 47), amoxicillin capsules (n = 45) and hydrochlorothiazide tablets (n = 43) were sourced from public and private sector healthcare providers. These products were subjected to in vitro dissolution, uniformity of weight and identity (Fourier Transformed Infrared Spectroscopy) tests using prescribed methods from the British (2005) and United States Pharmacopeias (2006). RESULTS: Respondents described drug quality in relation to the effect on symptoms. Procurement and use behavior of healthcare providers was influenced by prior experience, manufacturers' names and consumers' ability to pay. All formulations passed the in vitro tests for quality. CONCLUSIONS: This study showed clear differences between perceptions of quality and actual quality of medicines suggesting deficiencies in public engagement by government regarding the implementation of generic medicines policy. Implementation of generic medicines policy requires the involvement of consumers and healthcare providers to specifically address their information gaps and needs.

Assessment of crystalline disorder in cryo-milled samples of indomethacin using atomic pair-wise distribution functions.

The aim of this study was to investigate the usefulness of the atomic pair-wise distribution function (PDF) to detect the extension of disorder/amorphousness induced into a crystalline drug using a cryo-milling technique, and to determine the optimal milling times to achieve amorphisation. The PDF analysis was performed on samples of indomethacin obtained by cryogenic ball milling (cryo-milling) for different periods of time. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), polarised light microscopy (PLM) and solid state nuclear magnetic resonances (ss-NMR) were also used to analyse the cryo-milled samples. The high similarity between the γ-indomethacin cryogenic ball milled samples and the crude γ-indomethacin indicated that milled samples retained residual order of the γ-form. The PDF analysis encompassed the capability of achieving a correlation with the physical properties determined from DSC, ss-NMR and stability experiments. Multivariate data analysis (MVDA) was used to visualize the differences in the PDF and XRPD data. The MVDA approach revealed that PDF is more efficient in assessing the introduced degree of disorder in γ-indomethacin after cryo-milling than MVDA of the corresponding XRPD diffractograms. The PDF analysis was able to determine the optimal cryo-milling time that facilitated the highest degree of disorder in the samples. Therefore, it is concluded that the PDF technique may be used as a complementary tool to other solid state methods and that further investigations are warranted to elucidate the capabilities of this technique.

"This body does not want free medicines": South African consumer perceptions of drug quality.

OBJECTIVES Like many other developing countries, South Africa provides free medicines through its public health care facilities. Recent policies encourage generic substitution in the private sector. This study explored South African consumer perceptions of drug quality and whether these perceptions influenced how people procured and used their medicines. METHODS The study was undertaken in Durban, Cape Town and Johannesburg in South Africa between December 2005 and January 2006. A combination of purposive and snowball sampling was used to recruit participants from low and middle socio-economic groups as well as the elderly and teenagers. Data were collected through 12 focus group discussions involving a total of 73 participants. Interviews were tape-recorded. Thematic analysis was performed on the transcripts. RESULTS Irrespective of socio-economic status, respondents described medicine quality in terms of the effect the medicine produced on felt symptoms. Generic medicines, as well as medicines supplied without charge by the state, were considered to be poor quality and treated with suspicion. Respondents obtained medicines from three sources: public sector hospitals and/or clinics, dispensing doctors and community pharmacies. Cost, avoidance of feeling 'second-class', receiving individualized care and choice in drug selection were the main determinants influencing their procurement behaviour. Selection of over-the-counter medicines was influenced by prior knowledge of products, through advertising and previous use. Participants perceived that they had limited influence on selection of prescription medicines. Generic substitution would be supported if the doctor, rather than the pharmacist, recommended it. CONCLUSIONS Our findings emphasize the importance of meaningful consumer involvement in the development of national medicines policies, and strategic campaigns targeting consumers and prescribers regarding the quality of generic and essential medicines. Where consumers perceive free or generic medicines as inferior, this could significantly undermine attempts to implement national medicines policies aimed to improve access to medicines.

Drug quality in South Africa: perceptions of key players involved in medicines distribution.

PURPOSE: Substandard medicines contribute to poor public health and affect development, especially in the developing world. However knowledge of how manufacturers, distributors and providers understand the concept of drug quality and what strategies they adopt to ensure drug quality is limited, particularly in the developing world. The purpose of this paper is to explore pharmaceutical manufacturers', distributors' and providers' perceptions of drug quality in South Africa and how they ensure the quality of drugs during the distribution process. DESIGN/METHODOLOGY/APPROACH: The approach taken was qualitative data collection through key informant interviews using a semi-structured interview guide. Transcripts were analysed thematically in Johannesburg, Pretoria and Durban, South Africa. Participants were recruited purposefully from a South African pharmaceutical manufacturer, SA subsidiaries of international manufacturers, national distribution companies, national wholesaler, public and private sector pharmacists, and a dispensing doctor. In total, ten interviews were conducted. FINDINGS: Participants described drug quality in terms of the product and the processes involved in manufacturing and handling the product. Participants identified purchasing registered medicines from licensed suppliers, use of standard operating procedures, and audits between manufacturer and distributor and/or provider as key strategies employed to protect medicine quality. Effective communication amongst all stakeholders, especially in terms of providing feedback regarding complaints about medicine quality, appears as a potential area of concern, which would benefit from further research. ORIGINALITY/VALUE: The paper hightlights that ensuring medicine quality should be a shared responsibility amongst all involved in the distribution process to prevent medicines moving from one distribution system (public) into another (private).

Applications of terahertz pulsed imaging to sustained-release tablet film coating quality assessment and dissolution performance.

The potential of terahertz pulsed imaging (TPI) to predict the dissolution performance in sustained-release tablets was investigated in this study. Batches of coated tablets with similar weight gain during the coating process at the lab and pilot scales were subjected to non-destructive imaging by TPI and subsequently analysed by dissolution testing. The results from the dissolution tests revealed significant differences in the product performance between the lab and pilot scales (Student t-test, P<0.05). The model-independent dissolution parameters in the pilot scale showed a prolonged mean dissolution time. This indicated that the pharmaceutical active ingredient was released at a slower rate in the pilot compared to the lab scale. While weight gain measurements (the traditional coating quality parameter), failed to provide an early indication of the product functional performance; terahertz parameters (terahertz electric field peak strength and coating layer thickness) provided insight into the subsequent dissolution behaviour. Correlations between terahertz parameters and dissolution were much stronger than correlations between weight gain and dissolution; with the R(2) value for terahertz correlations typically around 0.84 as opposed to 0.07 for weight gain correlations. This study presents the initial finding of correlations between terahertz parameters for assessing the coating quality to the dissolution performance of the coated tablet. The contributing factors for these particular correlations are also discussed.