Non-destructive analysis of tulobuterol crystal reservoir-type transdermal tapes using near infrared spectroscopy and imaging

Sakamoto, Tomoaki; Fujimaki, Yasuto; Takada, Y; Aida, Kazunosuke; Terahara, Takaaki; Kawanishi, Toru; Hiyama, Yukio

doi:10.1016/j.jpba.2012.10.003

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…支持体上に展延したマトリックス型 1) の製剤で，中でも，皮膚に貼付するための粘着層に有効成分を含有するものが主流となっている．マトリックス型の製剤は，構造が単純で比較的容易に製造できること，製剤の厚みが抑えられることなどの利点があるが，薬物の安定性や放出性が基剤に大きく依存するため，基剤と薬物の相溶性や薬物の皮膚透過性，粘着力など，製剤設計には多面的な考慮が必要とされる． [2][3][4][5][6][7][8] 製剤設計においてマトリックス型貼付剤は，薬物が分子状態で基剤に溶解しているものと，溶解した薬物分子と薬物結晶が共存しているものの 2 種類に大別される．後者には，「結晶が薬物貯留槽となることで，膏体中の溶解した薬物濃度が，長時間にわたって一定に保持され，膏体から皮膚への持続的な放出がなされ」 9) るような特殊技術で製造された製品も流通しているが， [9][10][11][12] 製品数は限られる．このような，溶解した薬物分子と薬物結晶が共存している製剤において，薬物結晶の存在状態は放出速度の制御に関与することから，製品品質を保証するために管理されるべき重要な要素の 1 つと考えられる．ツロブテロール製剤では，結晶の分布状態や経時的な結晶の増加挙動を，ラマン分光法やテラヘルツ分光法，近赤外分光法を用いて解析した報告がみられる． [13][14][15] 一方，マトリックス型貼付剤の大多数を占める薬物溶解型の製剤では，体内への薬物移行性を高めるため，過飽和を利用した制御システムが多く試みられている． 16,17) このシステムは有効成分を，基剤に対する飽和溶解度を超えて含有させることで，製剤から角質層への拡散透過の駆動力が増加する仕組みを利用したものである．しかし，過飽和は熱力学的に不安定な状態であるため，基剤内における薬物の結晶化が問題となる． [2][3][4][5] 有効成分が基剤に溶解した状態で意図した効果が発揮されるように設計された製剤では，薬物の結晶化により皮膚透過性 [22][23][24][25][26] や粘着力 4,27,29) が低下することがある．結晶化に伴う放出性の低下を理由として，2008 年には米国でロチゴチン製剤が回収対象となった． 18,19) 中枢神経系や循環器に関連する疾患，がん性疼痛などの治療に用いられる全身作用性の経皮吸収型製剤は，経口剤や注射剤に代わる投与剤形と位置付けられており，薬物の体内移行性については厳密な制御が求められる．そのため，マトリックス型の経皮吸収型製剤の開発にあたっては，薬物が結晶化しにくい添加剤組成の検討が盛んに行われており， [29][30][31][32][33][34][35][36]…”

Section: 緒言現在流通している医療用貼付剤の多くは，基剤となる添加剤と有効成分を均一に混合してunclassified

Detection and Analysis of Drug Crystals in Medical Transdermal Patches by Using X-ray Diffraction Measurement

Miyazaki¹,

Aso²,

Goda³

2022

YAKUGAKU ZASSHI

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The crystallization of active pharmaceutical ingredients (APIs) in matrix-type transdermal patches has implications for the rate of drug absorption through the skin and patch adhesion strength. Therefore, the presence or absence and the degree of API crystallinity must be controlled to guarantee the quality of patches. In this study, the utility of laboratory-level X-ray diffractometers for the detection and analysis of crystalline APIs in transdermal patches was investigated using medical patches of tulobuterol and isosorbide dinitrate. Several matrix-type patches employ a controlled drug delivery system containing intentionally crystallized API. Both benchtop and high-resolution laboratory X-ray diffractometers can detect several characteristic peaks of the APIs in these patches even if the patches are wrapped in an outer bag, although a benchtop model provides peak heights one-seventh to onefifth that of a high-resolution instrument. An isosorbide dinitrate patch containing an unintentionally crystallized spot was wrapped in an outer bag, followed by measurements using both X-ray diffractometers. For both instruments, several isosorbide dinitrate-derived peaks were detected only at the crystallized spot, although the signal-to-noise ratio was poorer for the benchtop model. These results show that a high-resolution X-ray diffractometer is advantageous for high-detection sensitivity and offers a high degree of freedom of the measurement position on the sample. It was concluded that a laboratory-level high-resolution X-ray diffractometer can be used to examine the crystalline state of APIs in patches inside an unopened outer bag.

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Section: 緒言現在流通している医療用貼付剤の多くは，基剤となる添加剤と有効成分を均一に混合してunclassified

Detection and Analysis of Drug Crystals in Medical Transdermal Patches by Using X-ray Diffraction Measurement

Miyazaki¹,

Aso²,

Goda³

2022

YAKUGAKU ZASSHI

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“…The characterisation of pharmaceutical solid dosage forms (SDFs) using near infrared spectroscopy coupled with chemical imaging (NIR-CI) is extended to a wide range of applications related to quality control of end-products, e.g. active pharmaceutical ingredients (APIs) and excipient blending, [1][2][3][4][5][6][7] polymorphism, 8,9 counterfeit identification 10,11 and coatings. 12 NIR-CI and other hyperspectral imaging techniques based on vibration spectroscopy, like mid-IR, Raman and terahertz, are relevant due to the fast and non-invasive extraction of chemical information about the distribution of constituents in solid samples.…”

Section: Introductionmentioning

confidence: 99%

Classical Least Squares Combined with Spectral Interval Selection Using Genetic Algorithm for Prediction of Constituents in Pharmaceutical Solid Dosage Forms from near Infrared Chemical Imaging Data

Alexandrino

Breitkreitz

Poppi

2016

Journal of Near Infrared Spectroscopy

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A new algorithm that combines spectral interval selection using genetic algorithm and classical least squares (GA-iCLS) is presented for the prediction of the active pharmaceutical ingredients and excipients in various pharmaceutical solid dosage forms from near infrared chemical imaging data. The algorithm is based on the CLS approach, selecting the best wavenumber intervals in the unfolded hypercube of each sample (D), and in pure-compound reference spectra (S), wherein the pixel-to-pixel prediction capability of the compounds, obtained by C = DS T (SS T) −1 , is optimised for the samples. The wavelength intervals were selected (GA optimisation) while minimising the error between the mean concentrations of the ith compound predicted in the pixels and the nominal concentration in the corresponding sample (known a priori). The excluded wavenumber intervals from D (and S), for each sample, were interpreted based on systematic deviations from D = CS T + E (CLS approach) due to the scattering effects and/or intermolecular interactions in mixtures of the pure compounds. The comparison of the chemical images generated from the predictions performed using the GA-iCLS algorithms with similar images obtained without spectral interval selection, using direct CLS and multivariate curve resolution-alternating least squares, revealed the potential applicability of the proposed algorithm for analytical purposes for pharmaceuticals using chemical imaging data.

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Three-Dimensional Measurement of Ice Crystals in Frozen Materials by Near-Infrared Imaging Spectroscopy

Araki

Bae

et al. 2015

Drying Technology

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Non-destructive analysis of tulobuterol crystal reservoir-type transdermal tapes using near infrared spectroscopy and imaging

Cited by 5 publications

References 11 publications

Detection and Analysis of Drug Crystals in Medical Transdermal Patches by Using X-ray Diffraction Measurement

Detection and Analysis of Drug Crystals in Medical Transdermal Patches by Using X-ray Diffraction Measurement

Classical Least Squares Combined with Spectral Interval Selection Using Genetic Algorithm for Prediction of Constituents in Pharmaceutical Solid Dosage Forms from near Infrared Chemical Imaging Data

Three-Dimensional Measurement of Ice Crystals in Frozen Materials by Near-Infrared Imaging Spectroscopy

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