The Effect of Process Variables and Binder Concentration on Tabletability of Metformin Hydrochloride and Acetaminophen Granules Produced by Twin Screw Melt Granulation with Different Polymeric Binders

High-molecular-weight hypromellose (HPMC) and hydroxypropyl cellulose (HPC) are widely known, extended-release polymers. Conventional high-molecular-weight HPMCs are preferred in extended-release applications but not widely used in twin-screw melt granulation due to processability difficulties at low operating temperatures and potential drug degradation if high processing temperatures are used. Conversely, high-molecular-weight grade HPC (Klucel®) can be used in melt granulation processes. The purpose of this study was to evaluate the processability and dissolution behavior of HPC GXF ((Klucel® GXF) and a recently introduced type of hot-melt extrudable HPMC (Affinisol®) in extended-release metformin hydrochloride formulations using twin-screw melt granulation. Powder blends were prepared with 75% w/w metformin HCl and 25% w/w polymeric binder. Blends were granulated at processing temperatures of 160, 140, 120 and 100 °C. HPMC HME 4M (Affinisol® 4M) provided a fine powder, indicating minimum granulation at processing temperatures lower than 160 °C, and the tablets obtained with these granules capped during tableting. In contrast, acceptable tablets could be obtained with HPC GXF at all processing temperatures. Rheological studies including capillary rheometry to measure steady shear rate viscosity, and rotational rheometry to obtain time and temperature superposition data, showed that HPC GXF had a greater thermoplasticity than HPMC HME 4M, which made granulation possible with HPC GXF at low temperatures. Tablets compressed with granules obtained at 160 °C with both binders showed comparable dissolution profiles. High-molecular-weight HPC GXF provided a better processability at low temperatures and adequate tablet strength for the melt granulation of metformin HCl.

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Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2016.07.014 ◽

2017 ◽

Vol 106 (1) ◽

pp. 140-150 ◽

Cited By ~ 23

Author(s):

Amol Batra ◽

Dipen Desai ◽

Abu T.M. Serajuddin

Keyword(s):

Granulation Process ◽

Twin Screw ◽

Polymeric Binders ◽

Melt Granulation

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Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improvement in Compactibility of Drugs

10.26226/morressier.57d6b2bfd462b8028d88cfbd ◽

2016 ◽

Author(s):

Amol Batra

Keyword(s):

Granulation Process ◽

Twin Screw ◽

Polymeric Binders ◽

Melt Granulation

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Impact of hydrophilic binders on stability of lipid-based sustained release matrices of quetiapine fumarate by the continuous twin screw melt granulation technique

Advanced Powder Technology ◽

10.1016/j.apt.2021.05.040 ◽

2021 ◽

Author(s):

Dinesh Nyavanandi ◽

Venkata Raman Kallakunta ◽

Sandeep Sarabu ◽

Arun Butreddy ◽

Sagar Narala ◽

...

Keyword(s):

Sustained Release ◽

Quetiapine Fumarate ◽

Twin Screw ◽

Melt Granulation ◽

Sustained Release Matrices

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Influence of process variables on release properties of paracetamol tablets

Acta Pharmaceutica ◽

10.2478/v10007-007-0006-8 ◽

2007 ◽

Vol 57 (1) ◽

pp. 73-86 ◽

Cited By ~ 1

Author(s):

Gbenga Alebiowu ◽

Oludele Itiola

Keyword(s):

Interaction Effects ◽

Process Variables ◽

Factorial Experimental Design ◽

Disintegration Time ◽

Individual Effects ◽

Pregelatinized Starch ◽

Tablet Formulations ◽

Binder Concentration ◽

The Individual ◽

Paracetamol Tablet

Influence of process variables on release properties of paracetamol tablets A 23 factorial experimental design has been used to quantitatively study individual and interaction effects of the nature of binder (N), binder concentration (c) and relative density of tablet (d) on the disintegration time (DT) and dissolution times, t1, t50 and t90, of paracetamol tablet formulations. The factorial design was also used to study the quantitative effects of pregelatinization of starch binders on these parameters, i.e., N, c and d. In general, the most common ranking of the individual effects on DT, t1, t50 and t90 for native/native, pregelatinized/pregelatinized and native/pregelatinized starch binder formulations was c > d > N. For interaction effects, the most common ranking was N-c > c-d > N-d for all formulations. The results generally showed that c can considerably affect DT, t1, t50 and t90 of the tablets.

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