Using Metabolite Data to Develop Patient Centric Specification for Amide Impurity in Vildagliptin Tablets

Many specified impurities in vildagliptin's finished product have been disclosed in the literature that are above their qualification threshold. We used the impurity B (amide impurity) as a case example to explore whether existing literature can be leveraged to determine the safe level of impurity and thereby develop a patient-centric specification (PCS) for impurities. No-observed-adverse-effect level (NOAEL) was derived from rate metabolism information and converted to human equivalent dose (HED). The HED was estimated as 6.5 mg/day. The high qualification levels are supported by repeat dose toxicity studies performed in rats, mice and dogs. Maximum theoretical amount (MTA) was correlated with the maximum observed amount (MOA) to verify whether the exposure was due to impurity and/or metabolite. MOA/MTA was found ≥1 suggesting that metabolism contributed to the amount excreted in feces and therefore could be used to further justify a higher specification limit than the usual one of ≤0.5%. Quite often the drug metabolism and degradation pathways overlap, resulting in the formation of identical constituents. Therefore, metabolism data can be leveraged for deriving safe levels of degradation impurities and develop PCS for impurities.

Process Capability Analysis in a Polypropylene Bag Manufacturing Company

Process capability analysis combines statistical tools and control charts with good engineering judgment to interpret and analyze the data representing a process. This work analyzes the process capability of a polypropylene bag producing company. The case study organization uses two plants for production and data was collected over a period of nine months for this study. Analysis showed that the output spread of plant 1 was greater than the specification interval spread which implies poor capability. There are non-conforming parts below the Lower Specification Limit (LSL: 500,000 metres) and above the Upper Specification Limit (USL: 600,000 metres) and that the output requires improvement. Similarly, the capability analysis of plant 2 shows that the overall output spread is greater than the specification interval spread (poor capability). The output centre in the specification and overall interval are vertically aligned, thus specifying that the output from plant 2 is also process centered and requires improvement. Recommendations were made to improve the outputs from each production plant.

Microbial and heavy metals examination of Expellers groundnut (Arachis hypogaea L.) oil

This study was designed to determine the microbial and heavy metal contamination level in expeller’s groundnut oil. Ten samples of groundnut oil were collected, labeled from E1 to E10 and the microbial and heavy metals examination tests were laboratory assessed. The study results showed that, the Total Count of Bacteria (TCB) for all oil Expellers samples was 33.8 Colony Forming Unit (Cfu)/ml oil. The highestt value was (111 Cfu/ml) in E10 and the lowest value (7 Cfu/ml oil) in E1. Concerning the Total Count of Fungal (TCF) for all samples was 31.4 and 6.75 Cfu/1ml for the yeast and mould respectively. Yeasts highest count was 109 Cfu/ml in E10 and the lowest count was 6 Cfu/ml in E1. while moulds highest count was 18 Cfu/ml in E10 and the lowest number of 2 Cfu/ml oil was found in E2. The bacterial detection test of Staph, Bacillus, Coliform, and E.Coli in the oils Expellers explored that no bacterial presence in E1, E3, and E7 but, the four types were recorded in E5, E9 and E10. On the other hand E2, E6 and E8 showed positive detection to Staph and Bacillus, while E4 was positive to Bacillus detection only. The Concentration of Iron (Fe) on expeller oil samples (E2, E3, E4, E6, E7, E8, E9 and E10) was higher than the minimum specification limit of 5meq/kg for heavy metals, but E1 and E5 were within the minimum specification limit. All expellers oil samples were higher than acceptable limit for Copper (Cu) concentration that established by SSMO and Codex alimentary for heavy metals of less than 0.1meq/kg. As well as, the Concentration value of Lead (Pb) all expeller oil samples were above the specification limit of heavy metals that should not be more than 0.1meq/kg.

Mercury Determination in Certifiable Color Additives Using Thermal Decomposition Amalgamation and Atomic Absorption Spectrometric Analysis

Background Color additives requiring batch certification by the U.S. Food and Drug Administration (FDA) have Code of Federal Regulations (CFR) specification limits for certain elements and are usually analyzed by x-ray fluorescence spectrometry (XRF). However, sensitivity for Hg is too low in some color additives. Objective The thermal decomposition amalgamation-atomic absorption spectrometric (TDA-AAS) technique was investigated for providing quick and accurate determinations of Hg in certifiable color additives. Methods Tests were performed to optimize conditions and test reliability of Hg determinations at and below the CFR specification limit of 1 mg/kg. Results Sensitivity is much improved over XRF with limits of quantitation of 0.03 mg/kg for highly homogeneous color additives. Conclusions The TDA-AAS method can be used for determining Hg concentrations at and below the CFR specification limit. The technique is effective for all color additives, including those that are difficult to analyze by XRF, but less efficient for color additives that quickly deteriorate the catalyst. Regular quality checks using certified reference materials and in-house matrix-matched check standards are essential. Highlights The TDA-AAS method is applicable for use in routine color additive batch certification. Certain matrices (notably those that release nitrogen or sulfur oxides or halogens upon combustion) necessitate more frequent replacement of the catalyst and recalibration, impacting productivity. Color additives containing BaSO4, in color additive lakes, that are difficult to analyze by other techniques are well suited for TDA-AAS analysis.

Impurity Profiling of Baclofen Using Gradient HPLC–UV Method

The GABAB receptor agonist baclofen is a medication commonly used for the treatment of muscle spasticity. It is an amino acid and related to the neurotransmitter GABA. In this study, we developed a new, gradient high-performance liquid chromatography (HPLC) method for the impurity assessment of baclofen, which is appropriate for pharmacopoeial purposes. Since the impurities related to the synthesis pathway are acids, zwitterionic, or neutral, the method development is challenging. However, the separation of all components was achieved on a C18 stationary phase using a water–acetonitrile–trifluoroacetic acid gradient. A limit of detection (LOD) of at least 0.02% was registered for all specified impurities. Additionally, CAD detection was performed to detect potential impurities lacking off a chromophore. The baclofen batches analyzed are far more pure than expected. All impurities were found below the specification limit, and thus, they can be regarded as unspecified. Moreover, the required runtime could be significantly reduced compared to the current USP or Ph. Eur. method.

ANALISIS SIX SIGMA DENGAN DECISION ON BELIEF CHART PADA PRODUK HOT STRIP MILL

The Decision On Belief (DOB) control chart is a univariate control chart that was initially introduced as a solution to the problem of less than optimal control limits from the shewhart attribute diagram, especially the control chart C. The new scheme based on the DOB control chart is that the calculation step , can change the data which initially is not normally distributed into a normal distribution, then can diagnose quality control process errors. . defines belief or an assumption in the new observation vector and . The aim of this research is to apply the DOB control chart to data that is not normally distributed, so that it becomes a normal distribution. The result of the DOB control chart shows that the value of . is between the BKA and BKB values, which indicates a statistically controlled process. In this study, using one specification limit, namely the upper specification limit (USL) given by the company, which is 15 percent of the average production. The capability index used is for 3 sigma using the transformation result . Based on the sample data, the result shows that the value is 0.40633 and the sigma level is 2.719, so it can be concluded that the Hot Strip Mill production process is still not capable and has not reached the level of three sigma.Keywords: Six Sigma, Decision On Belief, capability index, , DPMO, level sigma.

Optimal decisions on fencing, pricing, and selection of process mean in imperfectly segmented markets

This paper integrates the selection of a process mean, production and marketing decisions at a firm’s level. We discussed a manufacturing firm’s problem that integrates its manufacturing decisions on production quantities and selection of a process mean with marketing decisions. The marketing decisions include setting prices, and the fencing investment to mitigate the effect of demand leakages between market segments. The manufacturing firm yields products of varied quality based on a single quality characteristic (e.g., amount of fill). The firm operates in a monopoly, and manufacturing process is assumed to follow a normal distribution, and therefore, it produces multi-grade (class) products distinct in their single quality characteristic. Depending upon the quality characteristic, a product with quality characteristic equal to greater than the upper specification limit is classified as grade 1 product, and sold in primary market at a full price. When the quality characteristic falls between the lower and the upper specification limits, it is referred to as a grade 2 product, and sold in a secondary market at a discounted price. Any product with a quality characteristic lower than the lower specification limit is reworked at an additional cost. A 100% error-free inspection is conducted to segregate the products at a negligible cost. Unlike many related studies in literature, this research proposes a novel integration of the pricing and production quantity decisions along with the process targeting in the two markets with pricing decision in the presence of demand leakages due to cross-elasticity. Furthermore, it is assumed that the firm can mitigate the demand leakage at an additional investment on improving fencing. Thus, the firm’s optimal decision would also include the pricing in each market segment, and fencing investment along with its decision on the production quantity for each product class. Mathematical models are developed to address this problem assuming the price-dependent stochastic demand. Structural properties of these models are explored and efficient heuristic solution methodologies are developed. Later, we also developed models when the stochastic demand information is only partially known, and proposed Harmony Search algorithm on the problem. Numerical experimentation is reported to highlight the importance of the proposed integrated framework and the impact of the problem related parameters on a firm’s profitability and its integrated optimal control decisions on selection of a process mean, pricing, production quantity, and fencing investment.

The Effect of Diffraction in the Degree of Bitumen Penetration on Asphalt Mixture Used for Surface Layer

Objectives: This research discuss the simulation of the bad bitumen which gives a penetration out of the specification limit and Study the effect of crumb rubber on the performance of asphalt mixture in case of low penetration grade and waste cooking oil in case of high penetration grade. Presentation of Case: Determination of the permissible limits of the diffraction in the degree of penetration for Suez Bitumen and Alexandria bitumen. Methodology: 14 asphalt mixtures are designed by using two types of bitumen (Alexandria bitumen and Suez bitumen). By using crumb rubber powder (C.R.P) with contents (6%, 8% and 10%) to decrease penetration for Alex bitumen by (59, 56 and 53) respectively. Then (-C.R.P-) was added with ratios (5%, 6.5% and 8%) to decrease penetration for Suez bitumen by (59, 56 and 53) respectively. after that waste cooking oil was added with different percentages (0.3%, 0.5% and 1%) for each bitumen type to increase penetration by (71, 74 and 77) respectively. Marshall Test was implemented for all asphalt mixtures to determine stability value and flow. The ITS Test was performed for all mixtures to determine tensile properties for mixtures. Results: The results were showed important conclusions for using bitumen with penetration grades (60/70) with increase or decrease in penetration by 7. Conclusion: This study recommends using (C.R.P) with ratios (10% and 5%) from bitumen weight for Alex and Suez bitumen respectively for achieving 53, 59 penetration to obtain 29% increase of stability value and 23.64% for Alex and Suez bitumen mixture respectively.