Impact of co-processed excipient particles solidity and circularity on critical quality attributes of orodispersible minitablets

The selection of appropriate functional co-processed excipient (CPE) is a crucial stage in orodispersible minitablets (ODMTs) development. This paper aimed to identify the most important morphological attributes influencing the flowability and homogeneity of powder mixtures and minitablets final quality. Our research included the use of the laser diffraction method, the microscopic automated imaging technique and a flowability tester.

Highlights

ODMTs technology requires perfect flowability and homogeneity of the powder mixture

Automated imaging technique provides crucial information on particle shape parameters

API micronization helps create a homogenous mixture with the co-processed excipients

Morphological analysis of co-processed excipients supports minitablets development

Solidity and circularity parameters influence on powder mixture homogeneity

All powder parameters examined were divided into two groups: those affecting mixture homogeneity or flowability. A Pearson’s correlation matrix revealed a strong relationship between both, especially in terms of solidity-circularity and convexity-circularity pairs (r = −0.71, p = 0.010 and r = 0.93, p = 0.000 respectively). An analysis of model mixtures confirmed that high solidity values of the CPE support final mixture homogeneity and accordingly high circularity values support its flowability. In conclusion, solidity and circularity were indicated as the most critical morphological parameters, which have to be analyzed to define the best possible ODMTs formulation.

Materials
The CPEs investigated for this paper were: Ludiflash® (BASF Group, Germany), Prosolv® ODT G2 (JRS Pharma, Germany), Pharmaburst® 500 (SPI Pharma Inc., USA), Parteck® ODT (Merck KGaA, Germany), PEARLITOL® Flash (Roquette Freres, France), SmartEx™ QD-50 and SmartEx™ QD-100 (Shin-Etsu Chemical Co., Ltd., Japan), F-Melt® Type M and F-Melt® Type C (Fuji Health Science, Japan), GalenIQ™ 721 (Beneo GmbH, Germany), Granfiller-D™ 211 and Granfiller-D™ 215 (Daicel Corporation, Japan). All excipients were kindly provided by the manufacturers. Vegetable magnesium stearate (FACI) was used as a lubricant. Micronized and non-micronized (coarse grade) melatonin (Flamma S.p.A., Italy) was used as the active pharmaceutical ingredient (API). The composition of each examined CPE is presented in the Supplementary Materials.

Conclusions
This paper demonstrated an application of automated microscope imaging for an extensive morphological assessment of commercially available co-processed excipients. The research aimed to evaluate the most critical attributes and investigate their influence on model powder mixtures behavior, as well as ODMTs characteristics. It also demonstrated the importance of solidity and circularity, which should be kept in mind at the preformulation stage, as well as the entire formulation development. Both attributes affect homogeneity and flowability of powder mixtures, which in turn affect critical ODMTs features, such as mean active substance content, mass variation, disintegration time and dissolution rate. It was proven that both attributes present a strong negative correlation. This means that the better the flowability, the lower the homogeneity of the powder blends. CPE should therefore be selected carefully, based on a simultaneous assessment of solidity and circularity predictors. This study investigated a group of twelve CPEs that are promoted individually in the market. A stage-by-stage analysis allowed us to select Granfiller-D 215 as the best excipient for ODMTs containing micronized melatonin. It should be highlighted that the remaining products were not rejected due to their poor quality, but this combination of CPE: API was the best one in presented case. It is however common knowledge that excipients should be chosen individually for a particular active substance. Applying different functional ingredients may be necessary to improve the powder flow, tablet disintegration time or improve tabletability. Therefore, each of the CPEs may be used to develop ODMT in a different composition. In the experiment described, a rigid approach was followed and all mixtures and tablets were made according to exactly the same procedure. This allowed to select one substance that turned out to be the best under these conditions. It was not our intention to promote any material. We believe that each of them is a really good commercial product and can be successfully used to obtain correct parameters for the end product. In each case, however, a different approach to the composition and selection of process parameters is necessary.

Read the full article here: Arkadiusz Hejduk, Sebastian Czajka, Janina Lulek, Impact of co-processed excipient particles solidity and circularity on critical quality attributes of orodispersible minitablets, Powder Technology, 2021