Harnessing ordered mixing to enable direct-compression process for low-dose tablet manufacturing at production scale

Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.

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Integrated modeling of a continuous direct compression tablet manufacturing process: A production scale case study

Powder Technology ◽

10.1016/j.powtec.2019.05.078 ◽

2019 ◽

Vol 354 ◽

pp. 199-210 ◽

Cited By ~ 6

Author(s):

S.C. Galbraith ◽

B. Cha ◽

Z. Huang ◽

S. Park ◽

H. Liu ◽

...

Keyword(s):

Manufacturing Process ◽

Integrated Modeling ◽

Direct Compression ◽

Production Scale ◽

Tablet Manufacturing

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Optimization of Microcrystalline Cellulose PH 101, Lactose, and Kollidon® K 30 To Obtain Co-Processed Excipient Through Spray Drying

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v7i2.8921 ◽

2017 ◽

Vol 7 (2) ◽

Author(s):

Kusuma P. ◽

Syukri Y ◽

Sholehuddin F. ◽

Fazzri N. ◽

Romdhonah . ◽

...

Keyword(s):

Spray Drying ◽

Microcrystalline Cellulose ◽

Chemical Change ◽

Direct Compression ◽

Flow Properties ◽

Scanning Calorimetry ◽

Compression Process ◽

Infrared Spectrophotometer ◽

Physical Mixtures ◽

Spray Dried

The most efficient tablet processing method is direct compression. For this method, the filler-binder can be made by coprocessing via spray drying method. The purpose of this study was to investigate the effect of spray dried co-processing on microcrystalline cellulose (MCC) PH 101, lactose and Kollidon® K 30 as well as to define the optimum proportions. Spray dried MCC PH 101, lactose, and Kollidon® K 30 were varied in 13 different mixture design proportions to obtain compact, free-flowing filler-binder co-processed excipients (CPE). Compactibility and flow properties became the key parameters to determine the optimum proportions of CPE that would be compared to their physical mixtures. The result showed that the optimum proportion of CPE had better compactibility and flow properties than the physical mixtures. The optimum CPE, consisting of only MCC PH 101 and Kollidon® K 30 without lactose, that were characterized using infrared spectrophotometer, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscope (SEM) indicated no chemical change therein. Therefore, this study showed that spray dried MCC PH 101, lactose and Kollidon® K 30 could be one of the filler-binder alternatives for direct compression process.

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Physico-Chemical and Pharmaco-Technical Characterization of Inclusion Complexes Formed by Rutoside with β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin Used to Develop Solid Dosage Forms

Processes ◽

10.3390/pr9010026 ◽

2020 ◽

Vol 9 (1) ◽

pp. 26

Author(s):

Teodora Balaci ◽

Bruno Velescu ◽

Oana Karampelas ◽

Adina Magdalena Musuc ◽

George Mihai Nițulescu ◽

...

Keyword(s):

Dissolution Rate ◽

Inclusion Complexes ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Molar Ratio ◽

Mechanical Resistance ◽

Direct Compression ◽

Active Ingredients ◽

Compression Process ◽

Antioxidant Power

The aim of our study was to obtain rutoside (RUT) inclusion complexes in β-cyclodextrin (β-CD) and in hydroxypropyl-β-cyclodextrin (HP-β-CD), in a 1:1 molar ratio, using the lyophilization method of complexation in solution. The complexes were confirmed and characterized, in comparison with the raw materials and their simple physical mixtures, by SEM, DSC, and FT-IR analyses. The antioxidant activity of the compounds was assessed by using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2’-azino-bis(3-ethylbenzothiazolin-6-sulfonic) acid (ABTS) radicals, determining the radical scavenging activity, and by ferric reducing antioxidant power (FRAP) assay. The results revealed superior antioxidant ability for the inclusion complexes towards rutoside alone. The inclusion complexes were used as active ingredients in formulations of immediate-release tablets. The preformulation studies were performed on the powders for direct compression obtained after mixing the active ingredients with the excipients (Avicel PH 102, Polyplasdone XL-10, magnesium stearate, and talc). The materials were assessed for particle size, flowability, compressibility, and moisture content, establishing they are suitable for a direct compression process. The tablets were characterized regarding their pharmaco-technical properties and the results proved that the formulations lead to high-quality delivery systems, showing a good mechanical resistance with a low friability, excellent disintegration times, and satisfying dissolution rate. The performances were very similar for both formulations and the physico-mechanical properties of the tablets are not influenced by type of the used cyclodextrin, but the RUT- HP-β-CD tablets presented a higher dissolution rate.

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FORMULATION OF RIZATRIPTAN BENZOATE SUBLINGUAL TABLETS PREPARED BY DIRECT COMPRESSION WITH DIFFERENT BIOADHESIVE POLYMER: IN VITRO AND EX VIVO EVALUATION

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10s4.21334 ◽

2017 ◽

Vol 10 (16) ◽

pp. 36

Author(s):

Harmanpreet Singh ◽

Pooja Jaiswal ◽

Suksham Gupta ◽

Simerjit Singh

Keyword(s):

Ex Vivo ◽

Methyl Cellulose ◽

Systemic Circulation ◽

Direct Compression ◽

Compression Process ◽

Rizatriptan Benzoate ◽

Dissolution Tests ◽

Ex Vivo Permeation ◽

Bioadhesive Polymers

Objective: The current investigation deals with formulation and evaluation of fast disintegrating sublingual tablets of rizatriptan benzoate (RTB) to produce its intended therapeutic effect for acute treatment of migraine. When the drug is given by sublingual route, it overcomes the first pass metabolism and quick entry of drug in systemic circulation is obtained. It would result in fast pharmacological response hence faster relief from migraine which is an important criterion in migraine therapy.Methods: In this study, RTB sublingual tablets were prepared using direct compression process using various bioadhesive polymers such as sodium carboxymethyl cellulose, hydroxyl propyl methyl cellulose-K4M, and chitosan at various concentration ranging 0.5-5% w/w along with sodium starch glycolate (SSG) or cross carmellose sodium (CCS) as super disintegrants at different concentration ranging 2-8% w/w.Results: The tablets disintegrated quickly and dissolution tests conclude that RTB was released from the formulation within the compendial limits. The formulations batches (A8 and B8) containing 2% w/w chitosan along with 2% w/w SSG or CCS which disintegrate rapidly and show high dissolution and ex vivo permeation were selected as optimized formulations.Conclusion: The results obtained from the study showed that the bioavailability problem of the drug has been solved as the drug is given by sublingual route and it directly enters into systemic circulation. Furthermore, the formulation overcomes the problems associated with migraine attack as fast disintegrating technology is used.

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Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

Pharmaceutics ◽

10.3390/pharmaceutics13111909 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1909

Author(s):

Emilia Jakubowska ◽

Natalia Ciepluch

Keyword(s):

Active Pharmaceutical Ingredient ◽

Content Uniformity ◽

Continuous Manufacturing ◽

Compression Process ◽

Factors Affecting ◽

Die Filling ◽

Drug Potency ◽

Tablet Press ◽

Tablet Manufacturing ◽

Processing Factors

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend homogeneity, or may result from further particle segregation during storage, transfer or the compression process itself. This review presents the most relevant powder segregation mechanisms in tablet manufacturing and summarizes the currently available, up-to-date research on segregation and uniformity loss at the various stages of production process—the blend transfer from the bulk container to the tablet press, filling and discharge from the feeding hopper, as well as die filling. Formulation and processing factors affecting the occurrence of segregation and tablets’ CU are reviewed and recommendations for minimizing the risk of content uniformity failure in tablets are considered herein, including the perspective of continuous manufacturing.

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PREFORMULATION STUDIES USING LACTOSE IN DEVELOPMENT OF SOLID ORAL DOSAGE FORM: A GRAPHICAL REPRESENTATION USING SeDeM METHOD

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017v9i5.22165 ◽

2017 ◽

pp. 168-172

Author(s):

Imran Tadwee ◽

Sadhana Shahi ◽

Zahed Zaheer

Keyword(s):

Dosage Form ◽

Graphical Representation ◽

Oral Dosage ◽

Direct Compression ◽

Compression Index ◽

Compression Process ◽

Lactose Monohydrate ◽

Anhydrous Lactose ◽

Good Compression ◽

Parameter Profile

Objective: The objective of the study is to evaluate and present lactose scientifically as an excipient of choice in formulation development of solid orals dosage form for direct compression method. Present work will establish the ability of lactose as an excipient to be the choice of candidate while developing formulation having poor flow API using direct compression process. In addition to this different type of lactose is processed using secure development method (SeDeM) in order to evaluate best suitable type of lactose amongst its different type.Methods: Lactose anhydrous, lactose monohydrate and Lactose spray dried (SD) were employed for evaluation using SeDeM method, twelve different selected pharmacotechnical parameters were determined experimentally and were treated mathematically and expressed in the graphical representation as SeDeM diagram. Parameter index, parameter profile index and good compression index values were calculated.Results: Good compression index was found to be 6.06,5.72,6.83 parameter index was 0.25, 0.42, 0.17 and parameter profile index found to be 6.36,6.01,7.18 for lactose anhydrous, lactose monohydrate and Lactose SD respectively.Conclusion: This research work reveals that data obtained will be useful for the pharmaceutical industries while formulating the drug product and will reflect the scientific characteristics of this excipient as well. This will enable the availability of values obtained after performing SeDeM studies on lactose to scientific society based on the results researchers can use establised data and statistics in their pre-formulation studies to incorporate lactose with confidence and can be justified scientifically in the development formulation of the direct compression process and API having poor flow. Results indicating good direct compression characteristics of the all 3 type of lactose, and Lactose SD can be preferred amongs these 3 types.Â

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