Effect of isomalt as novel binding agent on compressibility of poorly compactable paracetamol evaluated by factorial design

Sáska, Zs.; Dredán, J.; Balogh, Eszter; Luhn, Oliver; Shafir, G.; Antal, István

doi:10.1016/j.powtec.2010.03.009

Cited by 10 publications

(4 citation statements)

References 21 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Haı̈sa et al solved and refined the crystal structure of form I for the first time in 1976. This polymorph is commercially used in pharmaceutical formulations; however, it is not appropriate for direct compression − and requires a wet granulation process or the addition of several excipients − for tableting. Moreover, mixing paracetamol with some excipients can significantly decrease the rate of dissolution of the material, which has a direct effect on the bioavailability of the API …”

Section: Introductionmentioning

confidence: 99%

Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review

Cruz

Rocha

Ferreira

2019

Org. Process Res. Dev.

View full text Add to dashboard Cite

Paracetamol is a popular antipyretic and analgesic active pharmaceutical ingredient that is used worldwide in the production of several millions of tablets and other dosage forms every year. Paracetamol has three fully characterized polymorphs (forms I, II, and III), and also two high pressure polymorphs with unknown crystal structure (forms IV and V). Form I is the most stable polymorph, but unfortunately, it is not appropriate for direct compression into tablets due to its weak compression properties. On the other hand, forms II and III exhibit better compression properties; however, they are more difficult to harvest and isolate. This has been motivating the development of a diversity of crystallization methods that allow the selective production of forms II and III of paracetamol, which includes crystallization from melts, crystallization from liquid solutions, application of high pressures, seeding, heterogeneous nucleation, contact line crystallization, reaction coupling, ultrasound assisted crystallization, and multicomponent crystallization. In this review, we present a brief description of these methods and summarize their main advantages and disadvantages.

show abstract

Section: Introductionmentioning

confidence: 99%

Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review

Cruz

Rocha

Ferreira

2019

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…Isomalt is a well-tolerated, non-toxic polyol, which is traditionally used as a sweetening agent in the food industry and as a tabletting excipient for pharmaceutical purposes (Ndindayino, et al 2002;Sáska, et al 2010;Sentko and Willibald-Ettle 2012). Isomalt is included in the British (BP), the Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried lactate dehydrogenase

Tuderman

Strachan

Juppo

2018

International Journal of Pharmaceutics

View full text Add to dashboard Cite

The purpose of this research was to study isomalt as a protein-stabilizing excipient with lactate dehydrogenase (LDH) during freeze-drying and subsequent storage and compare it to sucrose, a standard freeze-drying excipient. Four different diastereomer mixtures of isomalt were studied. The stability of the protein was studied with a spectrophotometric enzyme activity test and circular dichroism after freeze-drying and after 21 days of storage at 16% RH. Physical stability was analyzed with differential scanning calorimetry and Karl Fischer titration. Statistical analysis was utilized in result analysis. LDH activity was almost completely retained after freeze-drying with sucrose; whereas samples stabilized with isomalt diastereomer mixtures had a considerably lower protein activity. During storage the sucrose-containing samples lost most of their enzymatic activity, while the isomalt mixtures retained the protein activity better. In all cases changes to protein secondary structure were observed. Isomalt diastereomer mixtures have some potential as protein-stabilizing excipients during freeze-drying and subsequent storage. Isomalt stabilized LDH moderately during freeze-drying; however it performed better during storage. Future studies with other proteins are required to evaluate more generally whether isomalt would be a suitable excipient for pharmaceutical freeze-dried protein formulations.

show abstract

“…One study determined that isomalt is also an option as diluent for orally disintegrating tablets [6]. Moreover, isomalt was found to be beneficial as excipient for wet granulation with acetaminophen [7]. …”

Section: Introductionmentioning

confidence: 99%

Compaction Behavior of Isomalt after Roll Compaction

2012

View full text Add to dashboard Cite

The suitability of the new isomalt grade galenIQ™ 801 for dry granulation and following tableting is evaluated in this study. Isomalt alone, as well as a blend of equal parts with dibasic calcium phosphate, is roll compacted and tableted. Particle size distribution and flowability of the granules and friability and disintegration time of the tablets are determined. Tensile strength of tablets is related to the specific compaction force during roll compaction and the tableting force. In all cases, the tensile strength increases with raising tableting forces. The specific compaction force has a different influence. For isomalt alone the tensile strength is highest for tablets made from granules prepared at 2 kN/cm and 6 kN/cm and decreases at higher values, i.e., >10 kN/cm. Tensile strength of the blend tablets is almost one third lower compared to the strongest tablets of pure isomalt. Friability of pure isomalt tablets is above the limit. Disintegration time is longest when the tensile strength is at its maximum and decreases with higher porosity and lower tensile strengths. Isomalt proves to be suitable for tableting after roll compaction. Even though the capacity as a binder might not be as high as of other excipients, it is a further alternative for the formulation scientist.

show abstract

Effect of isomalt as novel binding agent on compressibility of poorly compactable paracetamol evaluated by factorial design

Cited by 10 publications

References 21 publications

Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review

Application of Selective Crystallization Methods To Isolate the Metastable Polymorphs of Paracetamol: A Review

Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried lactate dehydrogenase

Compaction Behavior of Isomalt after Roll Compaction

Contact Info

Product

Resources

About