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.

Suplementación nutricional con omega 3 en retina: relación entre volumen y concentración en productos comerciales / Nutritional supplements with omega 3 in retinal disease: Relationship between volume and concentration in commercial products

OBJETIVO: Comparar las características morfométricas y la concentración de ácido docosahexaenoico (DHA) y ácido eicosapentanoico (EPA) de los diferentes suplementos nutricionales con omega 3 disponibles en el mercado para las dolencias de la retina. MATERIAL Y MÉTODOS: Estudio doble ciego, con observador único, de una muestra de diferentes comprimidos de suplementación de omega 3 comercializados en España. Se estudió tanto la longitud del comprimido como la concentración de omega 3 en total y de DHA y EPA por separado, utilizando para ello la cantidad proporcionada por el fabricante y el volumen de la cápsula calculado a partir del desarrollo de una fórmula específica para ello. RESULTADOS: Se incluyeron un total de 10 suplementos nutricionales diferentes. La media de omega 3 total, DHA y EPA fue de 383,10 ± 160,90; 210,72 ± 93,3 y 112,34 ± 140,98 mg, respectivamente. El tamaño medio de las cápsulas fue de 14,77 ± 0,19×8,13 ± 0,09 mm. La cápsula de menor tamaño fue la de Oftan mácula omega(R) (Esteve, Barcelona, España). Brudymacula(R) (Brudylab, Barcelona, España) y Brudyretina 1.5 g(R) (Brudylab, Barcelona, España) son las cápsulas con mayor cantidad de DHA. Nutrof omega(R) (Laboratorios Thea, Barcelona, España) es la que presenta menor concentración de omega 3, DHA y EPA por cápsula. CONCLUSIÓN: Existen diferencias importantes en cuanto a tamaño, volumen, cantidad y concentración de omega 3 y sus derivados entre los diferentes preparados comerciales. Solo el conocimiento de las características de los suplementos nutricionales nos permitirá la personalización de su indicación a nuestros pacientes

OBJECTIVE: To analyse the morphometric characteristics and the concentration of (docosahexaenoic acid) DHA and eicosapentaenoic acid (EPA) of the different nutritional supplements with omega 3 available on the market for retinal disease. MATERIAL AND METHODS: A double-blind study was conducted with a single observer, of the different omega 3 supplementation tablets sample marketed in Spain. The length of the tablet, the concentration of omega 3 in total, as well as DHA and EPA were studied separately using the amount provided by the manufacturer and the volume of the capsule calculated from the development of a specific formula for it. RESULTS: A total of 10 different nutritional supplements were included. The mean of total omega 3, DHA and EPA was 383.10 ± 160.90, 210.72 ± 93.3, and 112.34 ± 140.98 mg, respectively. The mean size of the capsules was 14.77 ± 0.19×8.13 ± 0.09 mm The smallest sized capsule was that of Oftan macula omega(R) (Esteve, Barcelona, Spain). Brudymacula(R) (Brudylab, Barcelona, Spain) and Brudyretina 1.5 g(R) (Brudylab, Barcelona, Spain) tablets contained more DHA, with Nutrof omega(R) (Thea Laboratories, Barcelona, Spain) having the lowest concentration of omega 3, DHA and EPA, per tablet. CONCLUSION: There are significant differences in size, volume, quantity, and concentration of omega 3 and its derivatives, between different commercial preparations. Only the knowledge of the characteristics of the nutritional supplements will enable us to provide a more personalised indication of their use for our patients

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.

Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus.

This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM), moisture content, Fourier Transform Infrared Spectrometry (FTIR), thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g) was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC.

Preparation and characterization of alginate and gelatin microcapsules containing Lactobacillus rhamnosus

ABSTRACT This paper describes the preparation and characterization of alginate beads coated with gelatin and containing Lactobacillus rhamnosus. Capsules were obtained by extrusion method using CaCl2 as cross linker. An experimental design was performed using alginate and gelatin concentrations as the variables investigated, while the response variable was the concentration of viable cells. Beads were characterized in terms of size, morphology, scanning electron microscopy (SEM), moisture content, Fourier Transform Infrared Spectrometry (FTIR), thermal behavior and cell viability during storage. The results showed that the highest concentration of viable cells (4.2 x 109 CFU/g) was obtained for 1 % w/v of alginate and 0.1 % w/v of gelatin. Capsules were predominantly spherical with a rough surface, a narrow size distribution ranging from 1.53 to 1.90 mm and a moisture content of 97.70 ± 0.03 %. Furthermore, FTIR and thermogravimetric analysis indicated an interaction between alginate-gelatin. Cell concentration of alginate/gelatin microcapsules was 105 CFU/g after 4 months of storage at 8 oC.

Quality of compounded hydrocortisone capsules used in the treatment of children.

OBJECTIVES: Due to the lack of paediatric-licensed formulations, children are often treated with individualized pharmacy-compounded adult medication. An international web-based survey about the types of medication in children with adrenal insufficiency (AI) revealed that the majority of paediatric physicians are using pharmacy-compounded medication to treat children with AI. Observations of loss of therapy control in children with congenital adrenal hyperplasia with compounded hydrocortisone capsules and regained control after prescribing a new hydrocortisone batch led to this 'real world' evaluation of pharmacy-compounded paediatric hydrocortisone capsules. METHODS: Capsule samples were collected randomly from volunteering parents of treated children suffering from congenital adrenal hyperplasia from all over Germany. Analysis of net mass and hydrocortisone content by high-performance liquid chromatography with ultraviolet (HPLC-UV) detection method was performed based on the European Pharmacopeia. RESULTS: In a total of 61 batches that were sent, 5 batches could not be analysed because of missing dose information, insufficient number of capsules or were not possible to be evaluated. Fifty-six batches containing 1125 capsules were evaluated. 21.4% of the batches revealed insufficiency in uniformity of net mass or drug content and additional 3.6% failed because they did not contain the labelled drug. CONCLUSIONS: Compounded medication is a possible cause of variation of steroid doses in children with adrenal insufficiency or congenital adrenal hyperplasia, putting these vulnerable patients at risk of poor disease control and adrenal crisis. These data may apply to other individualized compounded oral medication as well, emphasizing the need for development of licensed paediatric formulations approved by regulatory authorities.

Quality assessment of fluconazole capsules and oral suspensions compounded by pharmacies located in the United States.

OBJECTIVE To evaluate pharmaceutical characteristics (strength or concentration, accuracy, and precision), physical properties, and bacterial contamination of fluconazole compounded products. SAMPLE Fluconazole compounded products (30- and 240-mg capsules; 30- and 100-mg/mL oral suspensions) from 4 US veterinary compounding pharmacies. PROCEDURES Fluconazole compounded products were ordered 3 times from each of 4 pharmacies at 7- or 10-day intervals. Generic fluconazole products (50- and 200-mg tablets; 10- and 40-mg/mL oral suspensions) served as references. Compounded products were evaluated at the time of receipt; suspensions also were evaluated 3 months later and at beyond-use dates. Evaluations included assessments of strength (concentration), accuracy, precision, physical properties, and bacterial contamination. Acceptable accuracy was defined as within ± 10% of the labeled strength (concentration) and acceptable precision as within ± 10%. Fluconazole was quantified by use of high-performance liquid chromatography. RESULTS Physical characteristics of compounded products differed among pharmacies. Aerobic bacterial cultures yielded negative results. Capsules (30 and 240 mg) had acceptable accuracy (median, 96.3%; range, 87.3% to 135.2%) and precision (mean ± SD, 7.4 ± 6.0%). Suspensions (30 and 100 mg/mL) had poor accuracy (median, 73.8%; range, 53.9% to 95.2%) and precision (mean ± SD, 15.0 ± 6.9%). Accuracy and precision were significantly better for capsules than for suspensions. CONCLUSIONS AND CLINICAL RELEVANCE Fluconazole compounded products, particularly suspensions, differed in pharmaceutical and physical qualities. Studies to evaluate the impact of inconsistent quality on bioavailability or clinical efficacy of compounded fluconazole products are indicated, and each study should include data on the quality of the compounded product evaluated.

Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

BASICS OF COMPOUNDING: Capsules.

Capsules have been used for administering medications to patients more than a century and have an important role in drug delivery. When a primary care provider prescribes a tablet, the choice is usually, but not always, limited to commercially available products. A capsule, however, can be prepared extemporaneously, which provides dosing flexibility for the primary care provider and the pharmacist. This article discusses the definitions/types of capsules, their applications, composition, preparation, capsule sizes, the encapsulation process, capsule cleaning, physiochemical considerations, quality control in the preparation of capsules, packaging/storage, stability, and patient counseling to determine the proper capsule size. Also, provided are sample formulations.

Ease of opening of blistered solid dosage forms in a senior citizens target group.

Blisters differing in design and handling are established as packaging material for solid dosage forms. The ease of opening of blisters influences application and patient's compliance. In this study the influence of visibility and movability of solid dosage forms in blister packaging on both, easy opening and patient's satisfaction, were investigated by target group testing according to ONR CEN/TS 15945. For each testing 20 participants in the age of 65-80 years were recruited randomly. They opened the blisters on realistic terms without any auxiliary devices. Video documentation of the hands' movements was recorded to analyze the opening procedure. To show the influence of visibility of the dosage form in the blister, capsules size 1 were packed in transparent and opaque blisters. A moderate influence of the visibility on both, the ease of opening and patient satisfaction, was observed. A second study dealt with the movability of solid dosage forms in blisters. Therefore, three different sizes of tablets with similar shapes were packed in identical cavities. Limited movability was found as major criterion on effectiveness and effectivity of opening as well as on satisfaction with the opening procedure.

[Monitor on influence of quality standard improvement upon Guizhi Fuling capsules efficacy].

In 2012, the preparation process and quality standard for Guizhi Fuling capsule were improved. To compare the effects and differences of capsules before (2011) and after(2012-2014) the improvement, evaluation models for intrinsic dysmenorrhea, pelvic inflammation and hysteromyoma were applied in rats. Models were induced by oxytocin, liqiud bacteria mixture and estrogen loading, respectively. The capsules (12 batchs/year, 48 bathcs in all), sampled randomly in 2011-2014, the effects were assessed using the three models. In anti-dysmenorrhea models, remarked reduction of writhing frequency, ET-1 and PGF2α content in uterus could be detected, as well as extension of writhing latency. In pelvic inflammation rats, depression of TNF-α and raise of IL-2 were induced by earh batch of capsules. In hysteromyoma model, uterine weight and smooth muscle proliferation, including E2 and P level in plasma, were lowered obviously by all batchs of capsules. Secondly, Guizhi Fuling capsules produced in 2012-2014 revealed better effectiveness than the ones manufactured in 2011. Moreover, pharmacodynamics indexes of the samples made in 2011 differed significantly between groups, which could not be observed in the ones ot 2012-2014. After tne preparation process and quality standard improvement, the effectiveness and homogeneity of Guizhi Fuling capsules were enhanced.

Demonstrating evidence of acceptability: the "catch-22" of pediatric formulation development.

Both researchers and practitioners have reached an influential period in the new era of developing pediatric medicines. Evolving regulatory reforms and guidance continue to serve as platforms steering research and development while distinctive opportunities and challenges in the field emerge. An advancing research need involves gaining a better understanding of end-user requirements and acceptability of formulations. This review considers solid oral forms to demonstrate the importance of such research to stakeholders in policy and practice.

Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa®.

BACKGROUND: By definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson's disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians. METHODS: Madopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original "shelf-life" specifications in use by Roche. RESULTS: Each of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to -7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers. CONCLUSIONS: Deviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.

Difficulties swallowing solid oral dosage forms in a general practice population: prevalence, causes, and relationship to dosage forms.

PURPOSE: We assessed the prevalence of difficulties in swallowing solid oral dosage forms in a general practice population. Reasons, nature, and characteristics of tablets and capsules causing such difficulties were investigated as well as general practitioners' (GP) awareness of these difficulties. METHODS: A questionnaire survey was conducted in 11 general practices and consecutive patients taking at least one solid oral dosage form for ≥4 weeks were invited to respond to a questionnaire at the practices and one at home. Physicians completed a short questionnaire for each included patient. RESULTS: Of all participants (N = 1,051), 37.4 % reported having had difficulties in swallowing tablets and capsules. The majority (70.4 %) of these patients was not identified by their GP. The occurrence of swallowing difficulties was related to gender (f>m), age (young>old), dysphagia [adjusted odds ratio (adOR): 7.9; p < 0.0001] and mental illness (adOR: 1.8; p < 0.05). By asking "Do you choke while eating or drinking?", affected patients could be identified with a sensitivity of 62.6 % and a specificity of 78.1 %. Because of these difficulties, 58.8 % of the affected patients had already modified their drugs in a way that may alter safety and efficacy and 9.4 % indicated to be non-adherent. CONCLUSIONS: One in 11 primary care patients had frequent difficulties in swallowing tablets and capsules while GPs grossly underestimated these problems. Therefore, physicians should rule out swallowing difficulties regularly to avoid non-adherence and inappropriate drug modifications. Special attention should be paid to specific patient groups (e.g. women and patients with dysphagia, dysphagia indicators, or mental illness).

[Study on the quality standard of danmo capsule].

OBJECTIVE: To establish the quality standard for Danmo capsule. METHODS: TLC was used for the qualitative identification of Salviae Miltiorrhizae Radix Et Rhizoma and Lonicerae Japonicae Flos. HPLC was used to determine the content of Salvianolic acid B. RESULT: TLC spots were clear and well-separated without negative interference. The linear range of Salvianolic acid B was 0.120042 - 2.40084 microg (r = 0.9999) with an average recovery of 103.63%, RSD was 0.6% (n = 6). CONCLUSION: The method is simple, accurate and reliable. It can be used for the quality control of Danmo capsule.

Assessment of the quality of simvastatin capsules from compounding pharmacies.

OBJECTIVE: To validate a method for determining the simvastatin content of compounded capsules, using high performance liquid chromatography. METHODS: Eighteen samples of simvastatin 40 mg capsules from compounding pharmacies in the cities of São Paulo, Guarulhos, São Bernardo do Campo and Campinas, Southeastern Brazil, prescribed for fictitious patients were assessed. The analyses were based on the Brazilian Pharmacopoeia and on the high performance liquid chromatography method, optimized and validated in accordance with national and international standards for identification and quantification tests on compounded capsules. RESULTS: The mean weight of the capsules ranged from 70 mg to 316 mg; four samples presented weight variation outside of the specification. The simvastatin content in the capsules was within the specification in 11 samples. In six, the content ranged from 4% to 87% of the declared quantity, thereby not complying with the content requirements for the active agent. For one sample, no content or uniformity determinations were performed. In the content uniformity test, 15 samples presented indices of less than 85%, with relative standard deviations greater than 6%. Three pharmacies had met the specification in this test. In the dissolution test, eight samples presented unsatisfactory results in the first stage of the test, while the remainder presented inconclusive results. CONCLUSIONS: The method used was shown to be suitable for application to quality control, and it revealed the poor quality of the simvastatin capsules produced by some compounding pharmacies.

High failure rate of the dissolution tests for 500-mg amoxicillin capsules sold in Cambodia: is it because of the product or the test method?

OBJECTIVES: During the survey of substandard medicines in Cambodia in 2007, it was found that more than 90% of 500-mg amoxicillin (AMPC) capsules failed the United States Pharmacopeia (USP) 30 TEST 1 dissolution test. In the USP, several monographs provide multiple methods for performing the dissolution test. By using the 500-mg AMPC capsule as an example, we aimed to identify the problems and implications of the USP methods adopted for the dissolution test as a global standard. METHODS: All AMPC samples were collected from the Cambodian market in 2007. For the quantitative test, we referred to USP 30. We performed the USP 28 and USP 30 TEST 2 dissolution tests and compared these results with those of the USP 30 TEST 1. RESULTS: All 500-mg AMPC capsules used for the comparison passed the quantitative test. Samples that passed the USP 28 and USP 30 TEST 2 dissolution tests were identical, and the pass rate was 97.1% (34/35), whereas the pass rate with the USP 30 TEST 1 was 8.6% (3/35). The difference in the dissolution results between the three methods was significant (P<0.0001). CONCLUSION: This study revealed that many users would select the most stringent method when multiple methods exist in the USP. This may lead to a high failure rate of the tests. Because USP is a global standard, we recommend that it take into consideration the developing countries and create a more detailed user-friendly manual for selection for appropriate methods.

Quantification of microparticle coating quality by confocal laser scanning microscopy (CLSM).

In this work, a novel protocol was developed for determining film coating thickness and coating quality of microparticles, based on the use of confocal laser scanning microscopy (CLSM). CLSM was found to be an adequate non-destructive technique for the quantification of the coating thickness and coating quality of individual thin-coated small particles. Combined with image analysis, it was possible to derive with high accuracy the coating thickness distribution of a representative number of microparticles. The performance of the novel methodology was assessed by the quantification of the coating thickness and coating quality of protein-coated microparticles produced by fluidized bed coating. It was found that the CLSM data on coating layer thickness were generally in good agreement with the results from chemical analysis, down to a thickness of 1-1.5 microm. Using CLSM the importance of setting up the appropriate distance between the coating nozzle and the powder bed with respect to microparticle coating quality in fluidized bed processing was illustrated. Coating quality was found to decrease with increasing distance the coating droplets have to travel before impinging onto the core particles as a result of spray-drying of the coating droplets. Also, coating quality decreased with increasing viscosity of the coating droplets, resulting in reduced spreading on the cores.

Uniformity of weight test: a non-destructive test compared to the European Pharmacopoeia test.

The test for uniformity of weight as stipulated in the European Pharmacopoeia (Ph. Eur) is a complicated and time consuming method. The aim of the present project was to prove, that a new method developed in the Pharmacy Department of the University Hospital of Heidelberg is in principle equivalent to the Ph. Eur. method. Six lots of capsules were produced with a hand operated capsule filling machine. They were filled with mannitol and Aerosil. Three lots of capsules contained 0.5% Aerosil and the other three lots contained 5% Aerosil. Before filling the capsules, the lot specific empty capsule weight was defined in order to determine the real weight of contents. According to the Ph. Eur. method and our method the filling weight was calculated in two different ways. The results of both methods were compared always in relation to the real weight of contents of the capsules. The results suggested that the average filling weight of the Ph. Eur. method could never be well-defined because there is always substance left in the capsules when they are emptied in order to determine the empty weight. These findings demonstrated that our approach can be considered at least as good as the European Pharmacopoeia method. Furthermore the average filling weight of our method was more accurate which raises the question if the Ph. Eur. should be revised in this regard.