MEGGLE’s sieved, milled and micronized alpha-lactose monyhydrate for dry powder inhalation: InhaLac®

The delivery of active pharmaceutical ingredients (APIs) via the lung is becoming increasingly important as ever more patients all over the world suffer from chronic respiratory diseases [1].

Dry powder inhalers (DPIs) are widely used in pulmonary drug delivery. This is due to their advantages, such as ease of use, small size, portability, and the lack of requirement of breathactuation coordination [2]. Because they are propellant-free, they are environmentally friendly. Furthermore, as solid-particle formulations they are comparatively stable [3]. Usually, this dosage form contains a device, one or more APIs and an excipient that improves the powder qualities of the formulation. Features such as particle size are fundamental factors in the design of DPIs.

MEGGLE’s alpha-lactose monohydrate grades for inhalation effortlessly fulfill all criteria for achieving the desired quality, safety, and innovation of DPI formulations. Lactose has a long tradition of inhalation application and is proven safe. Thus, lactose is the excipient of choice in pulmonary drug delivery.

An established and well-documented production process has lead to this highly specialized product family called InhaLac®. In order to meet formulators’ expectations, this product family has a broad range. Sieved, milled, and micronized grades have excellent physio-chemical characteristics and conform with compendial requirements. Beyond that, a highly experienced team of specialists are waiting to support you in matters of processing and process adjustment.

Product description

In DPI formulations, the excipient not only acts as a filler
but also contributes to the performance features of the DPI. An extensive knowledge of the physio-chemical properties is a prerequisite to guarantee the functionality and safety of the DPI. This includes an established and well-investigated production process. All InhaLac® grades are produced via crystallization and subsequent sieving or milling. The optimized and standardized production process consistently ensures the highest production quality.

Depending on the API (concentration, particle size and shape, hydrophilicity, lipophilicity, …), the device (de-agglomeration principle, single- or multi-dose, capsule, blister, container, …) and the dosage-filling system, different formulation strategies must be applied to guarantee a high and repeatable delivery of the API to the lungs. As the different formulation principles require
distinct particle sizes of the excipient MEGGLE offers a range of sieved, milled and micronized InhaLac® grades.

Sieved InhaLac® grades
InhaLac® 70, the coarsest, sieved product, has a typical median particle size of approximately 215 µm, is virtually free of fines (particles < 15 µm), shows a narrow PSD (Span: 0.8) and is best suited to cyclone-based inhalation devices. InhaLac® 120 (median particle size: ~130 µm), InhaLac® 160 (median particle size: ~110 µm) and InhaLac® 230 (median particle size: ~100 µm), all three products have a narrowly distributed particle size (Span: ≤ 1.0) and a fines content between 3–5 %. InhaLac® 251, the finest sieved lactose grade, has a median particle size of approximately 50 µm. The product is characterized by a higher fines content (particles < 15 μm: > 10 %) and broader PSD.

InhaLac® 120, InhaLac® 160, InhaLac® 230 and InhaLac® 251 are mainly used in formulations for capsules or blisters (figure 1 and 2).

Milled/micronized InhaLac® grades
Besides the sieved InhaLac grades, with InhaLac® 140, InhaLac® 150 and InhaLac® 300 (figure 4 and 5) MEGGLE offers also three milled grades which are ideal carrier for capsule and blister based formulations. With the typical flow- and surface characteristic of milled lactose they provide an additional tool to tune and optimize the performance of the DPI product. InhaLac® 140 has a mean particle size of approximately 50 µm. InhaLac® 150 exhibits a narrow PSD with a typical x50 of around 24 µm. InhaLac® 300 is a lactose grade with 90% of the particles between 35 – 50 µm (Sympatec) or 40 – 56 µm (Malvern). The portfolio is completed by the blockbuster product InhaLac® 180. It features the frequently requested particle sizes of x10 5 – 25 µm and x50 50 – 100 µm.

InhaLac® 400 is a finely milled alpha-lactose monohydrate with a typical median particle size of x50 = 8 μm (figures 6 and 7). InhaLac® 500 is a micronized alpha-lactose monohydrate with a x90 ≤ 10 µm.

Therefore, InhaLac® 500 is well suitable for soft pellet formulations which are known as promising alternative for conventionally applied interactive mixtures for dry powder inhalation.

Further details about the specified particle size and typical values are shown in figures 3 and 8. All data was determined by laser light diffraction (Sympatec®/Helos & Rodos).