Excipient Selection in Oral Solid Dosage Formulations Containing Moisture Sensitive Drugs

Abstract

Moisture sensitivity of active pharmaceutical ingredients (APIs) presents a formidable challenge in the formulation of oral dosage forms. The interaction of moisture with APIs is crucial to an understanding of water-based processes, e.g. manufacturing or prediction of solid dosage form stability and shelf-life. Unwarranted moisture sorption by either APIs or excipients can result in unstable oral solid formulations. The appropriate selection of excipients for the core formulation and appropriate moisture barrier film coating helps to remedy the moisture-related issues with APIs and thus can improve the storage stability of the final formulations. In this chapter, we review the nature and extent of the moisture sensitivity and possible approaches taken to overcome it. Use of excipients that bind tightly with water reduce its potential interaction with the API. In addition, application of a barrier coating to reduce rate and extent of moisture ingress into the core of the solid dosage form during the storage (in original packaging or while in-use), are some of the many simple options that have been considered and described.Keywords Calorimetry · Degradation · Differential scanning calorimetry · Dynamic vapor sorption · Equilibrium relative humidity · Excipients · Isothermal microcalorimetry · Moisture · Moisture-barrier coating · Near-infra red Spectroscopy · Opadry · Optical waveguide spectroscopy · Packaging · Stability · Water · Water vapor transmission rate Abbreviations AluAluminum API Active pharmaceutical ingredient

Design, Optimization, and Correlation of In Vitro/In Vivo Disintegration of Novel Fast Orally Disintegrating Tablet of High Dose Metformin Hydrochloride Using Moisture Activated Dry Granulation Process and Quality by Design Approach

“…It could exhibit binding properties in the granulation applications, and then it would become a strong disintegrant when exposed to water owing to its ability to induce swelling. In addition, PGS had lower propensity for moisture uptake than sodium starch glycolate and croscarmellose sodium and drew less moisture into tablets [ 29 ]. Thus, it is a suitable binder/disintegrant for moisture sensitive drugs in granulation applications.…”

Stabilisasi Tablet yang Mengandung Zat Aktif Bersifat Higroskopis

“…Perlindungan kelembapan memainkan peran penting dalam stabilitas zat aktif selama pembuatan tablet [38] . Stabilitasi tablet yang sensitif terhaaldap kelembapan dapat dilakukan dengan berbagai cara seperti penggunaan eksipien, penyalutan dan pemilihan kemasan yang tepat dapat mempengaruhi kualitas tablet [18,27,39] .…”

“…Eksipien yang memiliki kapasitas tinggi untuk mengikat kelembaban terequilibrasi lebih lambat ke tingkat yang lebih tinggi dari mobile free water dan akibatnya menunjukkan kompatibilitas kimia yang lebih besar dengan zat aktif yang sensitif terhadap kelembapan dibandingkan eksipien dengan kapasitas pengikatan air yang lebih rendah. Hal ini dapat menghasilkan situasi dimana eksipien yang bersifat higroskopis dapat menstabilkan obat yang sensitif terhadap kelembapan [27] .…”

“…Bentuk sediaan padat farmasi dengan penyalutan adalah prosedur yang digunakan untuk berbagai tujuan seperti estetika, menutupi bau dan perlindungan dari kondisi lingkungan seperti kelembapan [27] . Bentuk sediaan akhir obat dengan penyalutan yang tepat memungkinkan untuk melindungi zat aktif yang bersifat sensitif terhadap kelembapan.…”

Formulation Strategies to Improve the Stability and Handling of Oral Solid Dosage Forms of Highly Hygroscopic Pharmaceuticals and Nutraceuticals

“…Many active pharmaceutical ingredients (API) and nutraceuticals (e.g., medicinal herbs, prebiotics, dietary fibres) are highly hygroscopic in nature in their solid form [ 1 ]. The high hygroscopicity causes multitude of issues such as alterations to their physicochemical properties, which in turn cause difficulties in subsequent downstream formulation processes, instability during their shelf life, and, eventually, adverse effects on their bioavailability [ 2 ]. Hygroscopicity, commonly known as ‘moisture-sensitivity’, can be defined as the susceptibility of a solid to absorbing or adsorbing and retaining water from their environment [ 3 ].…”