Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating.

Pharmaceutical tablets can be susceptible to damage such as edge chipping or erosion of the core during the tablet coating process. The intersection of certain process parameters, equipment design, and tablet properties may induce more significant tablet damage such as complete tablet fracture. In this work, a hybrid predictive approach was developed using discrete element method (DEM) modeling and lab-based tablet impact experiments to identify conditions that may lead to tablet breakage events. The approach was extended to examine potential modifications to the coating equipment and process conditions in silico to mitigate the likelihood of tablet breakage during future batches. The approach is shown to enhance process understanding, identify optimal process conditions within development constraints, and de-risk the manufacture of future tablet coating batches.

Diseño de estudios Gauge R&R cruzado y anidado para la validación de los modelos matemáticos de Heckel y Ryshkewitch-Duckworth / Design of crossed and nested Gauge R&R studies for the validation of the Heckel and Ryshkewitch-Duckworth mathematical models

INTRODUCCIÓN: Los estudios gauge permiten ganar información sobre el desempeño de procesos y son de utilidad para control de calidad, así como identificación de fuentes de variación. El objetivo del presente estudio, fue diseñar y analizar sistemas de medición para los modelos de Heckel y Ryshkewitch-Duckworth para caracterizar materiales, a través de estudios Gauge R&R. MÉTODO: Estudio Gauge R&R cruzado para evaluar el sistema de medición del peso y estudio Gauge R&R anidado para el sistema de la resistencia a la fractura. RESULTADOS: Ambos estudios cumplieron con los supuestos de normalidad, varianza constante e independencia de los datos, por lo que fue posible determinar la significación de las fuentes de variación (factores) mediante un ANOVA así como su porcentaje de contribución. Para el estudio Gauge R&R cruzado los punzones evaluados contribuyen a la variación de la medición de manera significativa y en un 97,38% de la variación total; los operadores contribuyen en menos del 1% y de manera no significativa y no existió interacción parte-operador. Respecto al estudio Gauge R&R anidado, se identificó que el operador no influyó de manera significativa en la variabilidad de la medición y que ésta es atribuible en un 95% a las diferencias existentes entre las tabletas evaluadas. CONCLUSIONES: Se realizó el diseño, ejecución y análisis de los sistemas de medición, destacando que en ambos estudios la principal fuente de variación fueron las partes evaluadas y que los operadores no contribuyen en la variabilidad de las mediciones, por lo que los estudios pueden usarse para evaluar los modelos matemáticos y durante el control estadístico de un proceso

INTRODUCTION: Gauge studies allow gaining information about the performance of processes and are very useful tools for quality control and identification of variability sources. The objective of the present study was design and analyzes measurement systems for the Heckel and Ryshkewitch-Duckworth models for characterizing materials, through Gauge R&R studies. METHOD: Crossed Gauge R&R study for the evaluation of weight measurement system and nested Gauge R&R study for the system of tablet hardness. RESULTS: Both studies fulfilled with the assumptions of normality, constant variance and data independence, therefore it was possible to estimate the significance of variation sources (factors) through ANOVA and their contribution percentage. The crossed Gauge R&R study showed that the flat punches contributed to variability of the measurement in a significant manner in 97.38% of the total variation of the study; operators did it in less than 1% and they were not statistically significant and there was no Part-Operator interaction. With respect to the nested Gauge R&R study, it was found that the operator did not influence in a statistically significant way in the variability of the measurement and it was attributable in 95% to the existing differences between the tablets evaluated. CONCLUSIONS: Design, run and analysis of the measurement systems was performed, we remark that in both of the studies the main source of variability were the parts evaluated and that operators did not contribute to variability in the measurements; therefore, both studies could be used to evaluate the Heckel and Ryshkewitch-Duckworth mathematical models and also for statistical process control

Comparative Quality Evaluation of Selected Brands of Cefuroxime Axetil Tablets Marketed in the Greater Accra Region of Ghana.

The ever-growing commercialization of poor-quality and substandard medicines, especially anti-infectives characterized by inadequate postmarket surveillance by stakeholders remains a major global health challenge, particularly in developing countries, where antibiotic drug resistance and its repercussions on human health remain dominant. This research sought to evaluate the pharmaceutical quality of six randomly selected brands of cefuroxime axetil tablets (250 mg) marketed in the Greater Accra region of Ghana. The selected brands were coded and subjected to both compendial and noncompendial tests. Statistical analysis and model-independent parameter (similarity factor, f2) were employed in analyzing the dissolution profiles of all the brands. All brands including the reference brand conformed to the pharmacopeial specifications for both compendial and noncompendial tests, indicating that they were of good quality. However, there were significant variations (p < 0.05) in the disintegration time amongst the various brands. All the brands had ƒ2 values > 50 indicating similarity of their drug release profiles with the innovator. Hence, all the sampled cefuroxime axetil brands can be considered as pharmaceutical equivalents to the innovator drug. These brands can, therefore, be used as a substitute for the innovator drug by physicians to patients in cases of unaffordability or unavailability of the innovator brand.

Do all colchicine preparations have the same effectiveness in patients with familial Mediterranean fever?

AIM: Colchicine is the primary treatment for familial Mediterranean fever (FMF). Several colchicine preparations are currently using available globally. This study aimed to describe the demographic, clinical, and genetic features of FMF patients treated with multiple colchicine preparations. MATERIALS AND METHODS: The records of patients diagnosed as FMF and followed-up by our pediatric rheumatology department were retrospectively evaluated. Patients that were treated with multiple colchicine preparations were included. Patient demographic, clinical, and laboratory data were obtained from the patient files and the hospital patient database. The daily colchicine dose and FMF attack frequency before and after switching from domestically produced (DP)-coated colchicine tablets to foreign produced (FP)-compressed colchicine tablets were compared. RESULTS: The study included 35 pediatric FMF patients (22 males and 13 females) with a mean age of 12.85 ± 4.62 years. Mean age at disease onset was 3.66 ± 2.11 years, versus 5.57 ± 4.28 years at diagnosis. The mean attack frequency before and after treatment with FP-compressed colchicine tablets was 9.50 ± 4.46 and 1.85 ± 1.41/year, respectively (p < .001). The mean attack duration significantly decreased in all the patients treated with FP-compressed colchicine tablets (p < .001). The difference in acute phase reactants during the attack-free periods before and after FP-compressed colchicine tablet treatment was significant (p < .001). CONCLUSION: The present findings show that pediatric FMF patients with ongoing attacks and elevated acute phase reactants during attack-free periods while treated with DP-coated colchicine tablets might benefit from switching to FP-compressed colchicine tablets before initiating biologic treatment. Long-term controlled studies are warranted, so as to obtain better evidence of the benefits of multiple colchicine preparations in pediatric FMF patients.

Quality Testing of Difficult-to-Make Prescription Pharmaceutical Products Marketed in the US.

Importance: Health care practitioners and patients must have information to support their confidence in the quality of prescription pharmaceuticals. Objective: To determine whether there were clear and substantive differences in major quality attributes between difficult-to-make solid oral dosage form pharmaceutical products marketed in the US. Design, Setting, and Participants: This quality improvement study analyzed US Food and Drug Administration-collected samples of 252 drug products marketed in the US and manufactured in the US, Canada, Europe, India, and the rest of Asia. These drug products were immediate-release solid oral dosage forms considered difficult to make on the basis of product quality history. This sampling included 35 innovator and 217 generic drug samples manufactured by 46 different firms containing 17 different active ingredients. Statistical analysis was performed from February to November 2019. Main Outcomes and Measures: All products were tested within their shelf life on the basis of the legally recognized tests of the US Pharmacopeia for the major quality attributes of dosage unit uniformity and dissolution. These tests measure dosage consistency and drug release, respectively. The consistency of either attribute was used to calculate a process performance index to describe the variability in manufacturing. Results: All 252 drug product samples met the US market standards for dosage unit uniformity and dissolution, although the process performance index (Ppk) for dissolution fell below the level of 4-sigma capability (ie, <1 error per 1600) for 11 different manufacturers and for generics in 4 of 5 regions, including the US. As part of a retrospective analysis, manufacturers performing above the median Ppk for either dissolution or dosage unit uniformity submitted fewer product quality defect reports (mean field alert reports of 0.22 and 0.63, respectively) than those falling at or below the median Ppk for these attributes (mean field alert reports of 2.1 and 1.7, respectively). Conclusions and Relevance: All samples met the US market standards for dosage unit uniformity and dissolution, indicating acceptability for use by patients regardless of manufacturer or region. To our knowledge, this is the largest sampling study of pharmaceutical manufacturers for the US market and these data provide objective insight into the quality of prescription drugs with high manufacturing risks.

Educating Patients by Providing Timely Information Using Smartphone and Tablet Apps: Systematic Review.

BACKGROUND: Patient education is a crucial element within health care. It is a known predictor for increased engagement in shared decision making, improved medication and treatment adherence, higher levels of satisfaction, and even better treatment outcomes. Unfortunately, often patients only remember a very limited amount of medical information. An important reason is that most patients are simply not capable of processing large amounts of new medical information in a short time. Apps for smartphones and tablets have the potential to actively educate patients by providing them with timely information through the use of push notifications. OBJECTIVE: The objective of this systematic review is to provide an overview of the effects of using smartphone and tablet apps to educate patients with timely education. Within this review, we focused on patients that receive their care in a hospital setting. We assessed the effects of the interventions on outcomes, such as patients' knowledge about their illness and treatment, adherence to treatment instructions and to medication usage, and satisfaction with the care they received. METHODS: A comprehensive search of MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Web of Science was conducted. Randomized controlled trials (RCTs) published between January 2015 and November 2019 were eligible for inclusion. Two reviewers independently searched and screened articles, assessed study quality and risk of bias, and extracted the data. Due to the heterogeneity of populations, interventions, and outcomes, a meta-analysis was not deemed appropriate. Instead, a narrative synthesis is presented. RESULTS: A total of 21 RCTs with 4106 participants were included. Compared to usual care, overall effectiveness of the interventions was demonstrated in 69% of the outcomes. Effectiveness increased to 82% when the intervention had a duration shorter than one month and increased to 78% when the intervention provided at least one push notification per week. The interventions showed the highest effects on satisfaction with information, adherence to treatment instructions and to medication usage, clinical outcomes, and knowledge. CONCLUSIONS: This review demonstrates that educating patients with timely medical information through their smartphones or tablets improves their levels of knowledge, medication or treatment adherence, satisfaction, and clinical outcomes, as well as having a positive effect on health care economics. These effects are most pronounced in interventions with a short duration (ie, less than a month) and with a high frequency of messages to patients (ie, once per week or more). With the knowledge that patient education is a predictor for improved outcomes and the fact that patients have obvious difficulties processing large amounts of new medical information, we suggest incorporating the delivery of timely information through smartphone and tablet apps within current medical practices.

Quantitative estimation of isoniazid content in the commercially available and government-supplied formulations.

BACKGROUND: Multi-drug resistant tuberculosis is on the rise, resulting in treatment failure. One potential reason for drug resistance is the substandard quality of manufactured antituberculous drugs. This study aims at finding out the difference in the quantity of isoniazid between government-supplied tablets and commercially available tablets. METHOD: Tablets from the single most commonly used brand of isoniazid manufactured by a pharmaceutical company and from RNTCP DOTS providing centre were obtained for the estimation of concentration using a spectrophotometer. The results were analysed using Un-paired Student's t-test. RESULTS: Of the 98 isoniazid tablets from each arm studied, none had the strength that deviated from the WHO limit of 90-110%, i.e. 270-330 mg. The mean strength ±SD of the commercial preparation of isoniazid tablets was found to be 295.16 ± 12.14. The mean strength ± SD of DOTS isoniazid tablets was found to be 298.69 ± 9.55. The difference observed in the strengths of isoniazid tablets between DOTS and commercial preparation was statistically insignificant (p = 0.1704). CONCLUSION: This method to estimate the strength of isoniazid tablets is inexpensive, relatively easy, and considerably accurate to perform, and hence can be employed in primary or secondary care centres to ensure the standard strengths of tablets dispensed from such centres.

Warpage optimization and influence factors analysis of 3D printing personalized JJY tablets.

To explore the feasibility of preparing traditional Chinese medicine using 3 D printing technology and reduce warpage commonly occurs in large-size tablets, we investigated the prescription, warpage optimization and influence factors of 3 D printing Jiuxiang Jianpi Yangwei (JJY) tablets. The procedures used conformed to the requirements of the 2015 edition of the Chinese Pharmacopeia. The results of the prescription screening showed that 75% ethanol and HPMC (9%) could be adhesives. Meanwhile, stevia (0.5%) and citric acid (0.5%) improved the taste of the 3 D printed JJY tablets. To ensure the quality and appearance of the printed tablets, the best parameters were as follows: drying at room temperature, 40% of the filling density, a 3 mm model height, two outer ring numbers and a printing speed of 15 mm/s. The optimized printed tablets had a smooth appearance, suitable hardness, with the weight uniformity in accordance with the Pharmacopeia. We also prepared personalized JJY cartoon tablets (which contained images of a big-headed pig and a small yellow duck) which were designed to increase the compliance of children when taking their medications. In conclusion, this study reported that 3 D printing technology has great potential for preparing traditional Chinese medicines, and it provided guidance for 3 D printing tablets without warpage.

Raman spectroscopy and mapping technique for the identification of expired drugs.

As expired medical products can be repackaged and sold by unscrupulous counterfeiters, it is essential to find a rapid and convenient method for distinguishing expired and unexpired drugs. Standard detection methods such as high-performance liquid chromatography (HPLC) and thin-layer chromatography are complex, time-consuming, and require organic solvents (that are environmentally unfriendly). Additionally, the Pharmacopoeia publications do not include information about identifying expired drugs. In this study, we proposed a novel method for identifying expired medications based on Raman spectra and verified it using >20 types of expired (Old) and unexpired (New) drugs, each type from the same manufacturer. A portable Raman spectrometer was used to collect Raman spectra of all samples and the similarities between the Old and New drugs (SN-O) were evaluated. Drugs with SN-O values <0.9 were classified directly as expired drugs. For drugs with SN-O values >0.9, the content of active pharmaceutical ingredient (API) might be so low (below or around 10 wt%) that its Raman signal is largely obscured by that of the excipients. In such cases, changes in the API content are undetectable using the portable instrument. Therefore, we adopted Raman mapping technology and established a virtual imaging map to locate areas of high API content. The similarities between the Old or New spectrum and that of the API (SO-A and SN-A, respectively) were calculated after removing the signal from the excipients. Our novel methods provide a precise, rapid, convenient, and environmentally friendly way to identify expired drugs that is more effective than the standard HPLC assay.

Bran of cassava starch flour and bran of cassava flour as potential tablet excipients / Salvado de harina y salvado de fécula de mandioca como potenciales excipientes para comprimidos

Objectives: The physicochemical characteristics of bran of cassava starch flour and bran of cassava flour (viz. organoleptic characteristics, pH value, moisture content, total ashes, lipid, protein, starch and fiber contents) and biopharmacotechnical parameters (viz. granulometry, flow capacity, angle at rest, outflow time and apparent density) were evaluated aiming at assessing their potential use as tablet excipients. Methodos: Three tablet formulations of venlafaxine hydrochloride were proposed, having as excipients bran of cassava flour, bran of cassava starch flour and Starch 1500(R). The tablets were produced using two different pressures (98 ± 5 MPa and 32 ± 6 Mpa) and their mechanical (hardness and friability) and dissol-ubility characteristics were evaluated. Results and Conclusions: The tablets produced with both cassava flours, using higher pressures, presented similar physicochemical characteristics to those obtained with the excipient Starch1500(R), thus indicating that cassava flours possess the potential to be used as disintegrating agents in tablets

Objetivos: Se evaluaron características físico-químicas del salvado de harina y del salvado de la fécula de mandioca (características organolépticas, pH, humedad, cenizas totales y contenido de lípidos, proteínas, almidones y fibras) y biofarmacotécnicas (granulometría, capacidad de flujo, ángulo en reposo, tiempo de salida y densidad aparente) con el objetivo de evaluar el uso de estos residuos como excipientes para comprimidos. Métodos: Se propusieron tres formulaciones en comprimidos de venlafaxina teniendo como excipientes salvado de harina de mandioca, salvado de fécula de mandioca y Starch 1500 (R). Las pastillas se produjeron utilizando dos presiones diferentes (98 ± 5 MPa y 32 ± 6 Mpa). Las características mecánicas (dureza y friabilidad) y de disolución de los comprimidos se evaluaron. Resultados y Conclusiones: Los comprimidos producidos con ambos salvados de mandioca, utilizando las presiones más elevadas, presentaron características físico-químicas similares a las obtenidas con el excipiente Starch1500(R), indicando que las harinas de mandioca poseen potencial para ser utilizadas como agentes desintegrantes en comprimidos

Quantitative fingerprint and quality control analysis of Compound Liquorice Tablet combined with antioxidant activities and chemometrics methods.

BACKGROUND: Herbal medicine (HM), as a complex system, is difficult to investigate their quality consistency effectively by chromatographic fingerprinting obtained in a single detection method. Moreover, active compound discovery affords no information about pharmacological activity until late in the discovery process, and the interaction between HMs in vitro is not yet clear, which requires sufficient practice to prove their effectiveness. PURPOSE: Therefore, the purpose of this study was to improve the quality control methods of Compound Liquorice Tablet (CLT) using multi-wavelength fusion fingerprinting, explore the possible antioxidant components and assess the interaction between herbs combined with bioactivity evaluation. METHODS AND DESIGN: Once the theoretical standard preparation obtained in combination of multi-wavelength fusion fingerprinting and hierarchical clustering analysis, averagely linear quantified fingerprint method could rapidly calculate the composition similarities and efficiently quantify the multiple components of CLTs without any chemical standard. Furthermore, the fingerprint-efficacy relationship was investigated by integrating high performance liquid chromatography fingerprints with antioxidant activity assessment using the partial least squares model, which was capable of directly discovering the bioactive ingredients. Hereafter, combination index value was introduced to evaluate the correlation between the two antioxidant herbs in CLT formula. RESULTS: The results showed that CLT samples were effectively identified and quantified, and their quality was accurately distinguished. By analyzing the antioxidant evaluation results, it was found that CLT had strong antioxidant activity, and through the study on PLS model and antioxidant activity assay of individual compounds, it was found that the order of chemical constituents responsible for antioxidant activity in CLT was as follows: flavonoids > saponins > alkaloids. Finally, it was determined that the CI value of GE-PPCE was in the range of 1.20-1.61, indicating that the interaction of the GE-PPCE pair was a slight antagonism. CONCLUSION: Thus, this study provided a preferred way for monitoring the quality consistency of HM, exploring possible bioactive components of HMs and assessing the interaction between herbs.

Development of a PAT tool for monitoring the Wurster coater performance.

Real-time process analytical technology (PAT) is proposed as an effective approach for monitoring the performance of a Wurster coater. The coater was used for coating of 0.78 mm pharmaceutical pellets. The coating solution consisted of Hydroxypropyl methylcellulose/Poly ethylene glycol. During the coating process, small amounts of pellets (∼2 g) were sampled at 10 min. intervals and the pressure fluctuations were recorded at the same time. The signals were analyzed using the wavelet transform (WT) and decomposed into different sub-signals. Principal component analysis (PCA) was employed to the energies of these sub-signals, whose outliers were eliminated using the Mahalanobis distance method. The reference coating thickness data were obtained via spectrophotometry during the coating process. The partial least squares (PLS) regression was incorporated with the PCA for the development of a model for prediction of the coating thickness. The PLS regression revealed that the pressure fluctuations can be used to evaluate the thickness with a good precision. This study demonstrated the applicability of pressure fluctuations for the prediction of the coating thickness. This method can be regarded as a new robust, fast and non-intrusive PAT approach for monitoring the coating process which can be easily used by engineers and practitioners.

Pediatric Oral Formulations: An Updated Review of Commercially Available Pediatric Oral Formulations Since 2007.

Oral pediatric formulations are either ready-to-use or require manipulation and multiuse or single-use. Strong encouragement for preservative-free pediatric formulations has resulted in fewer multiuse solutions or suspensions in favor of single-use solid oral dosage forms. This updated review covering new pediatric formulations marketed in the United States of America, Europe, and Japan spanning the years 2007 to mid-2018 identified 16 types of pediatric oral formulations of which 7 are ready-to-use and 9 require manipulation, and 51 total new pediatric oral formulations of which 21 are ready-to-use and 30 require manipulation. Ready-to-use formulations include oral solution, oral suspension, oral soluble film, tablet, scored tablets, orally disintegrating tablet, chewable tablet, and mini-tablets. Formulations requiring manipulation include sprinkle capsule, powder for oral solution, powder for oral suspension, granules for oral suspension, oral powder, oral granules, tablet, dispersible tablet, dispersible scored tablet, tablet for oral suspension, and mini-tablets (oral granules). Significant advances in packaging technology include filling mini-tablets, granules, or powders into sachets, stick packets, blisters, and 2-piece capsules. The future of pediatric oral formulations will increasingly be with user-friendly, preservative-free, taste-masked formulations including multiparticulate single-use solid dosage forms including mini-tablets, orally disintegrating tablets, and sprinkle capsules with or without a specialized package configuration.

Pharmaceutical quality evaluation of different glimepiride brands marketed in Karachi (Pakistan): In pursuance to global issue of availability and affordability of quality medicines.

Availability of economical quality medicines is always required for chronic disease management. Price differences among multiple brands of a product do not essentially displays low quality for the more affordable brand, however in a few occurrences it appears. Glimepiride, an oral anti-diabetic drug, is produced by several national and multinational industries in Pakistan with considerable cost variation. The study aimed to evaluate the quality and economy of various Glimepiride brands available in Karachi, specifically of public sector hospitals. For this, eight glimepiride brands were collected and analyzed for the pharmaceutical quality using physical parameters, disintegration test, dissolution profile, spectrophotometric assay and content uniformity. Pharmacoeconomic assessment was also carried out such as availability, affordability and price variation. A profound discrepancy was observed among the prices of selected brands. All of the products found to be equivalent to the reference product except G5, the most inexpensive and highest consumed product of a public sector hospital. Study concludes that products with higher quality and lesser price can be used as a substitute to the costly brands while availability of a substandard product looks for consideration of pertinent authorities to assure the distribution of quality medicines.

A Novel Forming Method of Traditional Chinese Medicine Dispersible Tablets to Achieve Rapid Disintegration Based on the Powder Modification Principle.

Slow disintegration and poor solubility are common problems facing the dispersible tablets of Traditional Chinese Medicine (TCM). In an early study, the research group found that co-grinding of extracts and silica could achieve a rapid disintegration effect, though the mechanism of this effect was not thoroughly elucidated. In this study, Yuanhu Zhitong dispersible tablets (YZDT) were selected as a model drug to explore the mechanism of rapid disintegration and dissolution. First, eight types of silica were used to prepare modified YZDT, and their disintegration time and amount of dissolution within 5 min were measured. Next, the powder properties of eight types of silica were investigated. By correlation analysis, it was found that the average pore size and density of silica were closely related to the effect of promoting disintegration. It was determined that the co-grinding of silica and extracts provided high porosity for the raw material drug, and its abundant narrow channels provided a strong static pressure for water penetration to achieve a rapid disintegration effect. Meanwhile, it was found that the addition of silica had a certain effect on promoting dissolution. Our results provide a highly operational approach for improving the disintegration and dissolution of TCM dispersible tablets. Meanwhile, this approach is also beneficial for establishing a high-quality evaluation index for silica.

Physicochemical quality profiles of commercial oral tablets and capsules containing lutein - impact of insufficient specific sanitary regulations.

Dietary supplements in many countries such as the USA do not require registration prior to commercialization. The Agência Nacional de Vigilância Sanitária (ANVISA) registers substances with functional properties as foods. Lutein is a carotenoid with antioxidant activity available on the market. However, no regulatory mandates exist to govern the design of quality control tests, which are necessary to ensure formulation effectiveness. Therefore, in the present study, tablet and dosage formulations from different manufacturers were tested following general methods outlined in the Brazilian and American Pharmacopeias. The averageweight, disintegration, content and dose uniformity assays were performed for all tablets and capsules, whereas hardness assays were only performed on tablets. None of the 10 formulations studied were found to be of satisfactory quality. Of all tablets tested, two had no-significant available lutein content, which may indicate adulteration. The capsules displayed adequate amounts of lutein, however had alarmingly negative disintegration and dissolution test results, which may contribute to non-bioavailability of lutein. All formulations analyzed are currently being marketed in the Brazilian and American markets. The low physicochemical performance in these formulations can be explained by the lack of specific regulations, which are necessary to ensure the quality of lutein-containing products on the market.

Sticking and Picking in Pharmaceutical Tablet Compression: An IQ Consortium Review.

Sticking and picking during tablet manufacture has received increasing interest recently, as it causes tablet defects, downtime in manufacturing, and yield losses. The capricious nature of the problem means that it can appear at any stage of the development cycle, even when it has been deemed as low risk by models, tests, and previous experience. In many cases, the problem manifests when transferring the process from one manufacturing site to another. Site transfers are more common now than in previous times because of the multinational nature of drug product manufacturing and the need for redundancy in manufacturing networks. Sticking is a multifactorial problem, so one single "fix" is unlikely to solve it completely, and "solutions" addressing one problem may exacerbate another. A broad-based strategy involving the API, formulation, tablet tooling, and the manufacturing process is the most likely approach to provide a robust and lasting solution. When faced with a sticking problem for the first or subsequent time, the formulator should address, in a structured way, a range of possible causes and remedies. In this article, we focus on current research and practice; on some of the common causes of sticking; mitigation and resolution strategies and solutions; and possible future directions in research.

Dissolution and uniformity of content of tablets developed with extract of Ximenia americana L.

Herbal medicines currently represent an important part of the world pharmaceutical market, which shows growing interest in the use of herbal medicines. However, the production of such medicines involves a complex series of steps, which determine the production viability and the quality of the final product. Ximenia americana L. is a plant occurring in several regions of the world, with well-known and applied medicinal properties. Thus, the aim of this work was to develop and evaluate the physical and physical-chemical quality of tablets produced with X. americana L. extract. The extract was spray-dried from a hydroethanolic extractive solution and characterized as to its phytochemical composition. The chemical marker was determined and quantified using validated chromatographic methods. These methods indicated the presence of gallic acid at a concentration of 1.61 mg g(-1). Formulations were proposed and analyzed for their flow and compaction properties. The best formulation was used to obtain a batch of tablets, which was evaluated for its quality characteristics and showed to be within the pharmacopoeial specifications for average weight, hardness, friability, and disintegration time. The dissolution profile of the tablets produced was obtained, showing the release of about 70% of the vegetable extract content within 30 minutes. Results showed that it was possible to obtain herbal tablets containing a high content of vegetal extract by direct compression, developing a rapid process of formulation and production and guaranteeing the quality characteristics of the final product.

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Orodispersible dosage forms: biopharmaceutical improvements and regulatory requirements.

Orodispersible dosage forms have a growing presence in the pharmaceutical market because their administration can improve the bioavailability of some drugs and their prescription can ameliorate patient adherence and/or compliance. Here, we review the main features of orodispersible tablets, including oral lyophilisates, and orodispersible films along with their main production technologies. We summarize the bioavailability data and critically discussed their potential to improve patient adherence and/or compliance. We revisit this information in light of both the European Union (EU) and US regulatory frameworks, focusing on the differences in the definitions of such dosage forms and the requirements for marketing authorization.