Methocel e5 premium lv

Hydroxypropyl methylcellulose (HPMC) inks with polymer contents of 12–18% were prepared as placebo formulations. HPMC (Methocel E5 Premium LV, Dow, Bomlitz, Germany) was dissolved in a deionized water and ethanol (Etax Aa 99.5%, Altia Oyj, Rajamäki, Finland) solvent mixture (1:1, v/v) using high speed mixing. Glycerol (CAS 200-289-5, Fagron GmbH & Co. KG, Glinde, Germany) (1%) was used as a plasticizer. Erythrosin B (spirit soluble 95%, CAS 16423-68-0, Aldrich Chem. Co., Milwaukee, WI, USA) was added (1%, v/w) as colorant to the formulations. Formulation development was continued with the formulation that contained 16% of HPMC. Lactic acid (LA, 1%, v/w) (CAS 50-21-5, Sigma-Aldrich, Japan), was added to the 1:1 ethanol water solvent mixture to lower the pH and consequently allow haloperidol (HAL, CAS 52-86-8, Sigma, China) to dissolve. Table 1 lists the various combinations of ink formulations that were studied.

Warfarin sodium clathrate (batch # WA22003; Alchymars Icm SM Private Ltd., Tamil, Nadu, India) was used as an active pharmaceutical ingredient. Microcrystalline cellulose (MCC) spheroids (CELPHERE™ CP-507 (500–710 µm); Asahi Kasei Co., Tokyo, Japan), dibasic calcium phosphate anhydrous (80 wt.%) and microcrystalline cellulose (20 wt.%) spheroids (PharSQ^® Spheres M (500–710 µm); Budenheim KG, Budenheim, Germany) [25 (link),26 ], and sodium chloride (NaCl; Valdo SIA, Riga, Latvia) sieved particles (500–800 µm fraction) were used as cores of pellets. Hydroxypropyl methylcellulose (HPMC; Methocel™ E5 premium LV; Dow Chemical, Midland, MI, USA) was used as a binder for drug loading (Figure 1A). Co-polymer comprising methyl methacrylate (MMA) and diethylaminoehtylmethacrylate (DEAEMA) in the ratio 7:3 in the form of aqueous dispersion Kollicoat^® Smartseal 30D (BASF SE, Ludwigshafen, Germany) was used as a taste-masking coating material (Figure 1B) [27 ] and dibutyl sebacate (DBS; Merck KGaA, Darmstadt, Germany) as a plasticiser [28 ]. A synthetic colloidal silicon dioxide (Syloid^® 244FP; Grace GmbH, Worms, Germany) was used as anti-tacking/-caking agent. Hydrochloric acid (37%), potassium dihydrogen phosphate, and disodium hydrogen phosphate (analytical grade) were supplied by Merck KGaA (Darmstadt, Germany).