Development of a Direct Compression Excipient from Epichlorohydrin-Crosslinked Carboxymethyl Rice Starch with Sodium Silicate Using a Coprocessing Technique

Abstract

A new, free‐flowing tablet disintegrant based on a coprocessed, cross‐linked carboxymethyl rice starch (CXO) is developed using a combination of chemical and physical modifications. Cross‐linked carboxymethyl starches are synthesized from an etherification between native rice starch and monochloroacetic acid and a cross‐linking reaction with epichlorohydrin with various ratios of the etherification reaction time to the cross‐linking reaction time (1:1, 1:0.67, and 1:0.33). The modified starches are then coprecipitated with 0–25% sodium silicate solution in methanolic solvent to obtain the CXOs. The physicochemical properties of the CXOs are characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffractometry, and differential scanning calorimetry. The solubility, swellability, moisture sorption capacity, and flowability parameters are also investigated and compared with those of native starch. A 10% sodium silicate solution is found to be best suited for coprocessing, yielding a modified starch (CXO‐12) with excellent flowability and compressibility. The lubricant sensitivity ratio of CXO (0.13) is 4–6 times lower than those of sodium starch glycolate (SSG) and croscarmellose sodium (CCS), and its dilution potential (11.2% w/w) is the best among the three excipients. The disintegration times of the model drug tablets containing CXO (16.83 ± 3.19 s) are not significantly different from those containing SSG (14.00 ± 2.45 s) or CCS (14.00 ± 2.83 s). A dissolution study showed that the drug release is greater than 80% after 15 min in the medium. These results suggest that CXO could be applied as a free‐flowing super disintegrant for direct compression processes.

A Spray-Dried, Co-Processed Rice Starch as a Multifunctional Excipient for Direct Compression

“…All other chemicals used were of AR grade or equivalent. Carboxymethyl rice starch cross-linked with ECH (CCMS) was prepared, as reported in our previous study [19]. The ratios of etherification reaction time to cross-linking reaction time was 1:0.67.…”

Artikel Review: Pengaruh Perlakuan Pada Pati Sebagai Superdisintegran Terhadap Waktu Hancur Fast Disintegrating Tablet

“…Berdasarkan Gambar 4. pati beras alami (a) memiliki bentuk polihedral yang tidak beraturan, sedangkan pati dengan koproses dan siliko dioksida (c) memiliki bentuk aglomerat bulat dengan permukaan halus, partikel kecil silikon dioksida teradsorpsi dan dapat terlihat pada permukaan partikel [33]. Ikatan silang karboksimetil pati beras (b) memiliki bentuk yang tidak beraturan, ukuran butiran kecil (5 nm) dan partikel sama dengan pati beras alami tetapi permukaan lebih bulat [34]. Permukaan yang menyusut pada pati ikatan silang karboksimetil ini terjadi karena efek dari alkohol dan air dalam persiapan proses koproses.…”

“…Dari semua pati yang dimodifikasi, ikatan silang karboksimetil merupakan salah satu pati yang paling banyak digunakan produk dalam industri makanan dan farmasi karena sifat pembengkakan, pengental dan pembentuk gelnya yang baik [57]. Pati hasil ikatan silang karboksimetilasi dengan POCl3 (fosforil klorida) [9], natrium trimetafosfat [35], epiklorohidrin [34] dapat meningkatkan hidrofilisitas air akibat penambahan bermuatan negatif (CH2COO -) [9], meningkatkan serapan dan kelarutan air pati dalam rantai induk pati [58] menyebabkan penetrasi air ke dalam granula pati meningkat dan pembengkakan granula pati. Ikatan silang karboksimetil pada pati nangka menghasilkan pati yang lebih higroskopis, kelarutan meningkat dibandingkan dengan pati nangka alami [35].…”

“…Ikatan silang karboksimetil pada pati nangka menghasilkan pati yang lebih higroskopis, kelarutan meningkat dibandingkan dengan pati nangka alami [35]. Modifikasi karboksimetil pati beras efektif meningkatkan pembengkakan, viskositas, sifat alir, dan kompresibilitas dibandingkan pati beras alami [34]. Kombinasi pati singkong pregelatinasi dan maltodekstrin DE 10-15 merupakan kombinasi modifikasi secara fisika dan enzimatis.…”

Formulation Study of a Co-Processed, Rice Starch-Based, All-in-One Excipient for Direct Compression Using the SeDeM-ODT Expert System

“…The CSs showed agglomerate spherical particles, thus improving the flowability of the material. The co-processing with CCMS, a superdisintegrant, provided rapid disintegration time of the co-processed tablet, while still preserving an adequate compressibility profile [11]. Nevertheless, CS needed more investigation to be applied in DC formulation.…”