(T1130-07-46) ZoomLab^®-Enabled Development of Directly Compressible Solid Dosage Forms with a Novel Co-processed Excipient

Purpose: Multifunctional excipients are gaining popularity in solid dosage form development, as they reduce the need to incorporate many excipients in a tablet blend, simplifying the formulation process. Co-processed excipients are among the multifunctional excipients, which enhance the formulation's performance and desirability. While individual excipients may not always deliver the intended outcomes during the manufacturing and development of a dosage form, researchers are working on producing multifunctional excipients with enhanced quality and cost-effectiveness to meet the needs of formulation scientists. This study intends to utilize the feasibility of one such novel co-processed excipient, Kollitab^TM DC 87 L, as a directly compressible (DC) excipient using different APIs and drug loads. This study also utilizes an advanced formulation algorithm-based platform, known as ZoomLab^®, which can predict an optimized dosage form design based on drugs’ physicochemical properties, route of administration, release profile, and compatibility with formulation excipients.

Methods: Kollitab^TM DC 87 L, an almost white, odorless, and free-flowing powder, was used to compress the tablets. It is a co-processed excipient based on lactose monohydrate (87%) [a filler], crospovidone (9%) [a super disintegrant], Kollicoat^® IR (3%) [a binder], and sodium stearyl fumarate (1%) [a lubricant]. ZoomLab^® (version 4.4) (a registered mark of BASF SE), was used to develop a directly compressible (DC) tablet containing Loratadine at a drug load (DL) of 10% and Kollitab^TM DC 87 L (90%). Based on the drug properties and physicochemical parameters, and after running multiple algorithms, ZoomLab^® suggested that a DC tablet was feasible for Loratadine with Kollitab^TM DC 87 L. Based on this, two more APIs namely Phenylephrine hydrochloride (10% DL), and Levocetirizine dihydrochloride (5% DL), were used to check the processability and compressibility of Kollitab^TM DC 87 L. All the tablets were punched on a carver-hand press, using a compression pressure of 2800 - 3200 lbf. Physicochemical characterization of the tablets included - DSC and XRD - to check the compatibility of the APIs with Kollitab^TM DC 87 L; Thickness - a way to determine dose uniformity and consistency; Hardness - to check the mechanical force that the prepared tablets can withstand during packing, shipping, and handling; Disintegration time - to check how quickly the tablets get dissociated into smaller particles, enabling dissolution of the drug; Dissolution - to determine the % drug release and content uniformity of the dosage form.

Results: DSC thermograms and XRD plots (Fig. 1A & 1B) revealed no interaction between the APIs, Kollitab^TM DC 87 L, and the powder blends. All the tablets had a thickness of 3.0 ± 0.1mm, thereby revealing a uniform dose. As can be seen in Table 1, the hardness of all the tablets (100-135N) was found to be well within the acceptance criteria for a directly compressible tablet. The disintegration time of the tablets was found to be within three to four minutes, which is ideal for an immediate-release tablet. Fig. 2 shows the dissolution profiles of Loratadine Tablets, Levocetirizine Dihydrochloride Tablets, and Phenylephrine Hydrochloride Tablets, illustrating that the developed tablets followed immediate release dissolution profiles, with more than 85% drug release within 15 minutes. The dissolution profiles also demonstrate that the drug was uniformly distributed in the dosage form. Further characterization studies are ongoing to assess the stability and in vitro-in vivo correlation (IVIVC) to predict their clinical outcomes.

Conclusion: In this study, we demonstrated the utility of a novel co-processed excipient, Kollitab^TM DC 87 L, using multiple APIs and at different drug loads. All the results lead to using this novel excipient as a best fit for direct compression, which will simplify the formulation development and shorten the processing time of blends.


Fig. 1: DSC Thermograms and XRD Graphs


Table 1: Formulae, Disintegration Time, and Hardness of the Tablets


Fig. 2: Dissolution profile of the Tablets