Exploring mixing uniformity of a pharmaceutical blend in a high shear mixture granulator using enthalpy values obtained from DSC

Segregation in particulate systems may be caused by particle size, density and shape distributions leading to negative effects on product quality as well as the production costs. Quantifying powder segregation using a reliable and robust method is challenging, particularly for low content level ingredients. In this paper, we evaluate the application of NIR spectral analysis for detecting the extent of segregation of components in a multi-component mixture. As a model system, a typical laundry detergent formulation, comprising spray-dried powder, known as Blown Powder (BP), Tetraacetylethylenediamine (TAED) and enzyme placebo granules, is used. The effect of using different pre-processing methods on the measured component fractions is analysed. These are scatter correction using Standard Normal Variate (SNV) as well as derivative correction using first, second, Norris-Williams and Savitzky-Golay derivatives. The results from the NIR technique are compared to those obtained by image analysis. Concepts of Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE) are used to evaluate the accuracy of different preprocessing methods. The second derivative of Norris-Williams method shows the best pre-processing method for the quantification of low content level enzyme placebo granules in the ternary mixture of detergent powder. Using the proposed NIR technique and the optimum pre-processing method, the segregation index of a low content level ingredient, such as enzyme placebo granules, is estimated to be 0.71 for a ternary heap of washing powders.

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“…effusivity is required for materials to evaluate the homogeneity of components using thermal methods [6][7][8][9].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Assessment of Near-Infrared (NIR) spectroscopy for segregation measurement of low content level ingredients

et al. 2017

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“…However, the group also agreed that when the sample size is small, alternative approaches may be acceptable. Therefore, a guidance for coefficient of variation (C v ), consistent with USP <905>, is followed in this work as has been done in numerous studies (Bharvada et al, 2015;Saffari et al, 2016;Yousaf et al, 2014). To characterize the blend uniformity, a precise method is important.…”

Section: Introductionmentioning

confidence: 99%

Improving blend content uniformity via dry particle coating of micronized drug powders

Huang

Xiong

Kunnath

et al. 2017

European Journal of Pharmaceutical Sciences

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Content uniformity of low dose blends with fine active pharmaceutical ingredients (API) is adversely impacted due to API agglomeration caused by high powder cohesion. Dry coating using high-intensity vibratory mixing is employed to reduce API cohesion and granular Bond number as well as agglomeration as predicted by contact models, hence improve blend content uniformity (CU). Micronized acetaminophen (mAPAP) (~10μm), a model API, was dry coated with nano-silica R972P (20nm), and mixed with Avicel 102. The amount of silica was varied from 0 to 2.74wt%, corresponding to theoretical surface area coverage (SAC) from 0 to 100% respectively. Bulk density, unconfined yield strength, and dispersive surface energy results indicated dry coating with 0.27 to 1.0wt% silica was adequate for API property enhancement; further corroborated by improved CU for 5wt% API blends. Excellent CU was achieved for 3, 5 and 10wt% API loaded blends, where 30min of mixing was found to be acceptable for all three. The CU with dry coated mAPAP was significantly lower and within the acceptable range as compared to control blends without silica, as well as those with silica added during blending. Sieving of mAPAP illustrated the reduction in mAPAP agglomeration, necessary for improved CU after dry coating, corroborating model based predictions. Compared to theoretical predictions, actual CU was higher unless API agglomerate size distribution obtained via sieving was taken into account. Overall, cohesion reduction by dry coating is shown as a promising approach for improving content uniformity of cohesive API blends.

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“…Було виготовлено модельні суміші за таких умов: вологість 15%, 20%, 30%, 40% та 50%, температура -від 15 °С до 25 °С з інтервалом 5 °С. Одержані таблетки досліджували за допомогою диференційної сканувальної калориметрії (ДСК) (прилад Q2000 TA Instruments, США), що реєструє тепловий потік, який характеризує фазові переходи в речовині в результаті зміни температури [4,5], термогравіметричного аналізу (прилад TGAQ500 TA Instruments, США), який дає змогу вивчити термічну стабільність препарату в широкому діапазоні температур [6], вагового методу визначення вологості (вологомір Shimadzu moisture balance MOC-120H, Японія). Результати порівнювали з даними, одержаними під час вивчення препарату порівняння Гептрал (Abbott SpA, Італія).…”

Section: м а т е р і а л и т а м е т о д и д о с л і д ж е н н яunclassified

Using the thermal methods of analysis in selecting the optimal production techniques for tablets based on ademetionine 1,4-butanedisulfonate substance

Burdak

Yarnyh

Yanchuk

et al. 2018

Farm Zh

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When developing tablets on the base of ademetionine 1.4-butandionsulfonat substance it is difficult to obtain a stable product, as substance is hygroscopic, and its quantity in the tablet is 90% by weight of the core. The aim of our work was the choice of conditions which would assure the safety of physical and chemical properties of the substance in the production process and allowed to get quality product. Tablet mass was prepared by dry mixing, controlling the relative humidity in the range from 15 to 50% and a temperature from 15 to 25 °C. Studies were carried out by differential scanning calorimetry and the method for determining the weight of moisture. The results were compared with those obtained in studies for comparing drug Geptral (Abbott SpA, Italy). As a result of studies was found that study samples number 1 and number 2 are as close as possible to their thermodynamic properties to the comparing drug. However, achieving a relative humidity of 15% is costly compared with values reaching 20%. Thus in the case of serial production is sufficient to create the following conditions: relative humidity not above 20%, the temperature +20,0 ± 2,0 °C.

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Exploring mixing uniformity of a pharmaceutical blend in a high shear mixture granulator using enthalpy values obtained from DSC

Cited by 13 publications

References 34 publications

Assessment of Near-Infrared (NIR) spectroscopy for segregation measurement of low content level ingredients

Assessment of Near-Infrared (NIR) spectroscopy for segregation measurement of low content level ingredients

Improving blend content uniformity via dry particle coating of micronized drug powders

Using the thermal methods of analysis in selecting the optimal production techniques for tablets based on ademetionine 1,4-butanedisulfonate substance

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