- Publikační typ
- tisková chyba MeSH
- Publikační typ
- tisková chyba MeSH
In recent years, CM has become increasingly popular in the pharmaceutical industry for the production of OSD forms. Most of the newly developed APIs nowadays are extremely cohesive and sticky with a mean particle size particle of <100 μm, a wide PSD and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed. Three challenging API (APAPμ, MPT and SD) and four different glidants (Aerosil® 200, Aerosil® R972, Syloid® 244FP and TRI-CAFOS® 200-7) were selected. For all feeding trials, a GEA CF equipped with 20 mm concave screws was used, in combination with an external catch scale. The volumetric feeding trials showed the ability of each glidant to increase the FFmax and reduce the FFmovRSD40 and the FFdecay for the cohesive APIs (APAPμ and MPT). Although the fumed silica grades showed the highest impact on the previously mentioned feeding parameters, low AE10 values were obtained, negatively affecting the feeding performance at higher glidant concentration. Both Syloid 244FP and TCP were good alternatives. However, to obtain a similar feeding performance a higher concentration of these glidants is required. The volumetric trials showed that glidant addition has no additional benefits for APIs with good flow properties such as SD. The second part of this paper discussed the impact of glidant addition on the gravimetric feeding behavior of the cohesive powders. Both the fumed silica grades (Aerosil® 200 and Aerosil® R972) and Syloid 244FP lowered the deviation on all LC% profiles of the cohesive APIs. In contrast to the volumetric trails, blends with excess fumed silica resulted in low AE10 values which are efficiently dosed by the CF during the gravimetric feeding.
- Klíčová slova
- Continuous direct compression, Continuous manufacturing, Flow enhancers, Formulation development, Glidants, Loss-in-weight feeding, Particle engineering,
- MeSH
- farmaceutická chemie metody MeSH
- farmaceutická technologie metody MeSH
- léčivé přípravky chemie aplikace a dávkování MeSH
- nerozplněné léky MeSH
- oxid křemičitý chemie MeSH
- pomocné látky * chemie MeSH
- příprava léků metody MeSH
- velikost částic * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- léčivé přípravky MeSH
- nerozplněné léky MeSH
- oxid křemičitý MeSH
- pomocné látky * MeSH
Nowadays, most of the newly developed active pharmaceutical ingredients (APIs) consist of cohesive particles with a mean particle size of <100μm, a wide particle size distribution (PSD) and a tendency to agglomerate, therefore they are difficult to handle in continuous manufacturing (CM) lines. The current paper focuses on the impact of various glidants on the bulk properties of difficult-to-handle APIs. Three challenging powders were included: two extremely cohesive APIs (acetaminophen micronized (APAPμ) and metoprolol tartrate (MPT)) which previously have shown processing issues during different stages of the continuous direct compression (CDC)-line and a spray dried placebo (SD) powder containing hydroxypropylmethyl cellulose (HPMC), known for its sub-optimal flow with a high specific surface area (SSA) and low density. Four flow-enhancing excipients were used: a hydrophilic (Aerosil® 200) and hydrophobic (Aerosil® R972) fumed silica grade, a mesoporous silica grade (Syloid® 244FP), and a calcium phosphate excipient (TRI-CAFOS® 200-7). The APIs and binary API/glidant blends (varied between 0.5-2.75 w/w%) were characterized for their bulk properties relevant for CDC. The results indicated that optimizing different bulk parameters (e.g., density, flow, compressibility..) of an API required varying weight percentages of the glidant (e.g., different surface area coverage (SAC)) depending on the APIs. Moreover, even at similar SAC, the impact of the glidant on the bulk characteristic of the APIs depended on the glidant type properties. While nano-sized silicon dioxide were effective for improving the flowability of a powder, other glidants (mesoporous silica and tricalcium phosphate (TCP)) showed also promise as alternatives. Additionally, an excess of glidant, referred to as oversilication, negatively impacted some bulk parameters, but other characteristics were unaffected. Finally, to determine the appropriate concentration of the different classes of glidants, SAC calculations, an understanding of the glidant's working mechanism, and knowledge about the API's characteristics (i.e., morphology, compressibility, flowability, aeration, density, and wall friction) are required. This study confirmed the necessity of including various material characterization techniques to assess the impact of glidants on the bulk characteristics of APIs.
- Klíčová slova
- Continuous manufacturing, Flow enhancers, Glidant, Material characterization, Rheological properties,
- MeSH
- deriváty hypromelózy * chemie MeSH
- farmaceutická chemie metody MeSH
- fosforečnany vápenaté * chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- metoprolol * chemie MeSH
- nerozplněné léky MeSH
- oxid křemičitý chemie MeSH
- paracetamol * chemie MeSH
- pomocné látky * chemie MeSH
- prášky, zásypy, pudry * MeSH
- příprava léků metody MeSH
- reologie * MeSH
- velikost částic * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- calcium phosphate MeSH Prohlížeč
- deriváty hypromelózy * MeSH
- fosforečnany vápenaté * MeSH
- metoprolol * MeSH
- nerozplněné léky MeSH
- oxid křemičitý MeSH
- paracetamol * MeSH
- pomocné látky * MeSH
- prášky, zásypy, pudry * MeSH
