(M1130-06-39) Biosustane as a Novel Oral Excipient for Solid Dosage Forms – Formulation Development, Characterization, and IVIVC Prediction

Purpose: The FDA has approved around 100,000 oral drug products, but only 231 excipients are available for oral dosage forms. Most small drug molecules (75-80%) require functional excipients to address the associated physicochemical challenges, including bioavailability improvement through solubility and permeability enhancement. Polyfunctional excipients, such as Biosustane (sucrose acetate isobutyrate, SAIB), play multiple roles, including solubility improvement, bioavailability enhancement, mucoadhesion, and formation of amorphous solid dispersions. Additionally, Biosustane is FDA-approved for injectable bupivacaine (POSIMIR®) and is considered safe for oral drug delivery for humans. Despite challenges like high viscosity and stickiness, Biosustane shows significant potential as a novel excipient for oral drug delivery. Besides software-based simulations, tools such as IVIVC Plus™ from GastroPlus, the Phoenix IVIVC Toolkit from Certara are instrumental in developing, validating, and predicting pharmacokinetic parameters. These capabilities are essential for formulating clinically enabled drug products. For Biopharmaceutics Classification System (BCS) Class II drugs, where dissolution is the main rate-limiting step for absorption, these tools help establish in vitro–in vivo correlation (IVIVC). By doing so, IVIVC model able to predict of a drug's behavior in the human body, thus supporting more efficient and rational drug development. This study explores the feasibility and potential of Biosustane as a one-stop excipient in developing clinically relevant oral solid dosage forms of Quetiapine (QTP), a BCS Class II drug.

Methods: QTP granules were developed using two different concentrations of Biosustane: 21.74% and 13.04%, using solvent evaporation and wet granulation methods. The drug-loaded formulations, QD22% and QE13%, contained 43.48% quetiapine hemifumarate, with the remainder comprising lactose (diluent), sodium lauryl sulfate (surfactant), and magnesium stearate (lubricant). In parallel, control formulations QDC22% and QEC13% were prepared without the active drug, replacing quetiapine with lactose to maintain equivalent formulation percentage, allowing for comparative evaluation. The prepared granules were evaluated for flowability via the Carr Index and the Hausner ratio. Physicochemical characterization was performed using various techniques, including DSC, XRD, SEM, and TGA. Tablets were compressed by the Carver laboratory press (Model-C, Fred S. Carver Inc., USA) using QD22% and QE13% granules. In-vitro dissolution was conducted using a USP-II Dissolution apparatus following the dissolution gradient method, in 900 ml of dissolution media at 37.0±0.3°C, with the paddle rotating at 100 rpm. Both formulations (QD22% and QE13%) were also tested for scalable manufacturing using STYLone equipment, and compressed tablets (QD22%) were tested for dissolution. Stability studies were performed following the ICH guidelines over a period of 1 month. An IVIVC model was developed to predict clinical performance based on the innovator drug product (Seroquel®) in vitro dissolution and respective clinical data with Gastroplus 9.9. The model validation was completed following FDA IVIVC guidance.

Results: The solubility of QTP was significantly improved by 63% when combined with Biosustane compared to aqueous solubility. Formulations were optimized using 22% SAIB (with and without quetiapine) via the solvent evaporation, and 13% SAIB (with and without quetiapine) following wet granulation. Both processes generated granules with good flow properties, suitable for solid dosage forms (Table 1). Granules from QD22%, QDC22%, QE13%, and QEC13% were analyzed using DSC, XRD, SEM (Fig. 1), and TGA (Fig. 2), revealing that the formulations were more amorphous than the pure drug. The presence of 43.48% API did not alter granule properties, confirmed by the control batches QDC 22%, and QEC 13% (Fig. 1). Tablets compressed from QD22% and QE13% showed almost identical dissolution profiles, releasing 80% of the drug within 1 hour. Stability testing under accelerated conditions showed no change in dissolution rate up to 1 month (Fig. 2). Tablets compressed for QD 22% with STYLone also exhibited a similar dissolution profile, compared to lab-scale tablets. The IVIVC model was developed and validated according to FDA guidance. As per Fig. 3, the validation results demonstrated that the prediction error for Cmax was below 10%, indicating high accuracy in predicting peak plasma concentrations. Furthermore, the Area Under the Curve (AUC) prediction error was also within an acceptable range (≤15%), reinforcing the reliability of the model. The percentage prediction error for Cmax and AUC remained within the established limits, demonstrating an excellent correlation between in-vitro dissolution data and in-vivo pharmacokinetic performance. We simulated the in-vitro dissolution data of the QD22% formulation using the IVIVC model. The model revealed that the small intestine is the primary site for drug absorption. For the 100 mg tablets, the model predicted a high absorption rate of 93.1%, indicating the drug is highly absorbed in the gastrointestinal tract. For the Pharmacokinetic (PK) Prediction, QD22% predicted a Cmax of 0.183 µg/mL and an AUC of 1.536 µg-h/mL for the human.

Conclusion: QTP solid oral dosage form with Biosustane was formulated, characterized, and an IVIVC was established, predicting human absorption and pharmacokinetic parameters. In conclusion, using Biosustane to develop clinically viable solid dosage forms is practically feasible

Acknowledgements: Thanks to Eastman company for providing the Biosustane samples, and BASF to provide the trial opportunity for using the STYLone compression machine.


Fig 1: Formulations, Process, flowability tests, DSC,PXRD,and SEM of the granules


Fig 2: TGA and moisture content of the granules, In vitro dissolution evaluations



Fig 3: IVIVC model development, validation , simulation for the human absorption and pharmacokinetic parameters prediction of the QD22%