RetaLac® – MEGGLE’s co-processed hypromellose lactose excipient for direct compression

Modified release applications continue to be a development strategy for the global pharmaceutical industry. Products nearing patent expiration are candidates for product life-cycle management using this approach; however, other benefits such as improved efficacy through more structured active pharmaceutical ingredient (API) release profiles, cost effective product manufacture, and improved patient compliance exist. With various options available for API modified release delivery, hypromellose (hydroxypropyl methylcellulose or HPMC) has historically been the excipient of choice to form hydrophilic matrices [1]. The basic structure of the commonly known methyl and hydroxypropyl mixed ether of cellulose is illustrated in figure 1.

In the hypromellose chemical structure diagram (shown below), the substituent “R” may represent a hydrogen atom, or the methoxy or hydroxypropyl functional groups, which when substituted onto the cellulose backbone, form the hypromellose structure. The degree of substitution as well as the molecular weight affect the physiochemical properties.

To define the level of methoxy or hydroxypropyl degree of substitution, the major global pharmacopoeias (Ph. Eur., USP-NF, and JP) differ with four defined hypromellose species (1828, 2208, 2906, 2910), classified according to their relative degree of substitution: the irst two digits indicate the percentage of methoxy groups, while the subsequent two digits represent the percentage of hydroxypropyl groups. Exacting limits for the degree of substitution have been established. In addition, there is a method to determine average chain length by evaluation of apparent viscosity.

Hypromellose grade 2208, with a nominal viscosity of roughly 4000 mPa·s (2 % solution, 20 °C), may be regarded as a very frequently used grade in modified release formulation development and manufacture.

Although hypromellose offers broad flexibility in tailoring API release due to differing substitution levels and molecular weights, processability is generally limited to traditional labour, time, and energy intensive wet granulation manufacturing methods.

Particle size distribution (PSD)

Figure 2 shows typical laser diffraction particle size distribution analysis for RetaLac®, MEGGLE’s co-processed hypromellose/ lactose excipient. Results show a typical x10, x50 and x90 of 55, 150 and 260 μm, respectively.

Isotherms

Due to the hypromellose content, RetaLac® shows a tendency to absorb moisture at elevated relative humidity, as shown by dynamic vapor sorption (figure 3). Interrestingly, the equivalent physical admixture maintains a largely similar behaviour to RetaLac® (not shown).