Assessment of Crystallinity in Processed Sucrose by Near‐Infrared Spectroscopy and Application to Lyophiles

Luner, Paul E.; Seyer, Jeffery J.

doi:10.1002/jps.24007

Cited by 7 publications

(3 citation statements)

References 53 publications

(93 reference statements)

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“…Chemically, the absorption peaks observed between 8700 cm À1 and 7700 cm À1 ; peaks observed between 7200 cm À1 and 5200 cm À1 ; between 5200 cm À1 and 4200 cm À1 are due to CH second overtones, OH first overtones and CH þ OH combination bands, respectively. 22 The sharp peak observed between 7200 cm À1 and 6700 cm À1 is due to crystalline sucrose, 23 Fig. 1A.…”

Section: Near Infrared Spectroscopy (Nirs) and Chemometrics Based On Pcamentioning

confidence: 93%

Quantitative Microscopy: Particle Size/Shape Characterization, Addressing Common Errors Using ‘Analytics Continuum’ Approach

Saravanan

Muthudoss

Khullar

et al. 2021

Journal of Pharmaceutical Sciences

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Particle size/shape characterization of active pharmaceutical ingredient (API) is integral to successful product development. It is more of a correlative property than a decision-making measure. Though microscopy is the only technique that provides a direct measure of particle properties, it is neglected for reasons like non-repeatability and non-reproducibility which is often attributed to a) fundamental error, b) segregation error, c) human error, d) sample randomness, e) sample representativeness etc. Using the "Sucrose" as model sample, we propose "analytics continuum" approach that integrates optical microscope PSD measurements complimented by NIR spectroscopy-based trending analysis as a prescreening tool to demonstrate sample randomness and representativeness. Furthermore, plethora of statistical tests are utilized to infer population statistics. Subsequently, an attribute-based control chart and bootstrap-based confidence interval was developed to monitor product performance. A flowchart to serve as an elementary guideline is developed, which is then extended to handle more complex situations involving API crystallized from two different solvent systems. The results show that the developed methodology can be utilized as a quantitative procedure to assess the suitability of API/excipients from different batches or from alternate vendors and can significantly help in understanding the differences between material even on a minor scale.

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Section: Near Infrared Spectroscopy (Nirs) and Chemometrics Based On Pcamentioning

confidence: 93%

Quantitative Microscopy: Particle Size/Shape Characterization, Addressing Common Errors Using ‘Analytics Continuum’ Approach

Saravanan

Muthudoss

Khullar

et al. 2021

Journal of Pharmaceutical Sciences

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“…6,8 Excipients in lyophilized solids can also be adversely affected by residual moisture. For example, sucrose can undergo recrystallization 9 or hydrolysis if the matrix is sufficiently acidic. 10 In general, low residual moisture is favored for lyophilized protein products.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For example, water can be directly involved in chemical degradation reactions by serving as a reactant (e.g., hydrolysis) or can affect reactions indirectly by changing the dynamics or conformational stability of the protein. , At high moisture content, proteins also tend to be more susceptible to various physical degradation processes such as denaturation and aggregation. , Excipients in lyophilized solids can also be adversely affected by residual moisture. For example, sucrose can undergo recrystallization or hydrolysis if the matrix is sufficiently acidic . In general, low residual moisture is favored for lyophilized protein products .…”

Section: Introductionmentioning

confidence: 99%

Photolytic Labeling To Quantify Peptide–Water Interactions in Lyophilized Solids

Chen

Topp

2019

Mol. Pharmaceutics

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Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide “KLQ” (Ac–QELHKLQ–NHCH3) was covalently labeled with NHS–diazirine (succinimidyl 4,4′-azipentanoate), and the labeled peptide (KLQ–SDA) was formulated and exposed to UV light in both solution and lyophilized solids. Solid samples contained the following excipients at a 1:400 molar ratio: sucrose, trehalose, mannitol, histidine, or arginine. Prior to UV exposure, the lyophilized solids were exposed to various relative humidity (RH) environments (8, 13, 33, 45, and 78%), and the resulting solid moisture content (Karl Fischer titration) and glass transition temperature (T g; differential scanning calorimetry, DSC) were measured. To initiate photolytic labeling, solution and solid samples were exposed to UV light at 365 nm for 30 min. Photolytic-labeling products were quantified using reversed-phase high-performance liquid chromatography (rp-HPLC) and mass spectrometry (MS). In lyophilized solids, studies excluding oxygen and using H2 18O confirmed that the source of oxygen in KLQ adducts with a mass increase of 18 amu are attributable to reaction with water, while those with a mass increase of 16 amu are not attributable to reaction with either water or molecular oxygen. In solids containing sucrose or trehalose, peptide–excipient adducts decreased with increasing solid moisture content, while peptide–water adducts increased only at lower RH exposure and then plateaued, in partial agreement with the water replacement hypothesis.

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Vibrational Spectroscopy

2017

Solid State Properties of Pharmaceutical Materials

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Assessment of Crystallinity in Processed Sucrose by Near‐Infrared Spectroscopy and Application to Lyophiles

Cited by 7 publications

References 53 publications

Quantitative Microscopy: Particle Size/Shape Characterization, Addressing Common Errors Using ‘Analytics Continuum’ Approach

Quantitative Microscopy: Particle Size/Shape Characterization, Addressing Common Errors Using ‘Analytics Continuum’ Approach

Photolytic Labeling To Quantify Peptide–Water Interactions in Lyophilized Solids

Vibrational Spectroscopy

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