Phage Dosage Form Design Services

Background

Phage dosage form design is a critical aspect of developing effective phage therapies. The design of dosage forms must ensure the stability, efficacy, and deliverability of bacteriophages while minimizing degradation and maximizing patient compliance. Various dosage forms, including liquid, semi-solid, and solid formulations, have been explored for phage therapy, each with unique advantages and challenges.

Different Dosage Forms

• Liquid Dosage Forms: Liquid formulations are favored in phage therapy for easy preparation and use. Buffers like SM help maintain phage stability. Stabilizers such as trehalose, sucrose, or glycerol improve storage viability. Suitable for intravenous, intramuscular, and topical use.
• Semi-Solid Dosage Forms: Creams, gels, ointments, and pastes deliver phages to skin, wounds, and mucosal surfaces. Base choice affects phage stability—non-ionic bases creams preserve viability better than ionic ones. Uniform phage distribution is key for consistent effect.
• Solid Dosage Forms: Suppositories, lozenges, and encapsulated phages allow controlled release and protection. Encapsulation boosts stability and targeting. Ideal for mucosal delivery (rectal, vaginal, oral). Design must consider melting point, dissolution, and comfort.

Figure 1. Different phage dosage forms. (Adapted from Briot et al., 2022)

Encapsulation and Microencapsulation Techniques

Encapsulation techniques, such as spray drying, freeze-drying, and microencapsulation, are used to protect phages from environmental factors and enhance their stability. For example, spray-dried phages with trehalose or skim milk as stabilizers have shown good viability and stability. Microencapsulation using sodium alginate and calcium chloride can further protect phages and control their release.

Figure 2. Phage encapsulation methods. (Loh et al., 2021)

Considerations for Dosage Form Design

• Stability: Formulations must stay stable during storage and use. Buffer, pH, and stabilizers are key.
• Compatibility: Must suit both phage and target tissue. Ionic interactions can impact efficacy.
• Patient Compliance: Application ease, taste, and comfort matter, especially for solid/semi-solid forms.
• Manufacturability: Scalable methods must ensure even distribution and phage viability. Geometric dilution aids uniformity.

Creative BioMart Microbe offers phage dosage form design services, providing end-to-end formulation solutions customized for each phage candidate and therapeutic objective. By integrating virology, pharmaceutics, and delivery system engineering, we support the creation of stable, scalable, and application-specific phage dosage forms. For more information or to request a quote, please contact us.

Service Procedure

Service Details

• Initial Consultation: We assess your phage type, delivery goals, stability concerns, and regulatory requirements to define the project scope.
• Formulation Planning: A customized strategy is developed based on phage characteristics, route of administration, release profile, and storage expectations.
• Prototype Creation: We prepare initial dosage form samples—such as capsules, gels, suspensions, or powders—tailored to your target delivery method.
• Stability Testing: Formulations are tested for phage viability, physical stability, and compatibility with excipients under various storage conditions.
• Optimization & Scale-Up: The best formulations are refined for improved performance, longer shelf life, and manufacturing feasibility at larger scales.
• Final Report Delivery: You receive a full development report, including composition, preparation method, test results, and next-step recommendations.

Dosage Forms Supported

Our Advantages

• Tailored to Phage Biology: Formulations are designed to preserve infectivity and structural integrity across diverse phage morphotypes and delivery routes.
• Multimodal Delivery Capabilities: We support oral, injectable, topical, rectal, and inhalable phage dosage forms with delivery profiles adapted to each application.
• Gastrointestinal Protection Strategies: Advanced encapsulation techniques and pH-sensitive coatings protect phages from gastric acid for targeted intestinal release.
• Stability-Driven Formulation Design: Our strategies maximize shelf life through lyophilization, cryopreservation, and excipient compatibility testing under ICH conditions.
• Formulation to Scale-Up Ready: Prototypes are engineered with downstream scalability in mind, facilitating the transition from bench to pilot production.
• Integrated with Phage Analytics: Our in-house phage QC testing ensures formulation performance is guided by precise infectivity and purity data.

Case Study

Case Study 1: Semi-solid and solid dosage forms for the delivery of phage therapy to epithelia.

Phage delivery to epithelial surfaces is a promising therapeutic approach currently under clinical evaluation. This study examines research on formulating phages into semi-solid forms (like creams and ointments) and solid forms (such as lozenges and suppositories) for targeted epithelial application. It highlights key considerations around formulation stability, efficacy, and the selection of suitable delivery bases, while emphasizing the need for standardized formulation and testing methods to ensure consistent, comparable results.

Figure 3. P. acnes phage PAC1 stability in semi-solid dosage forms. These regression plots show 4 °C (as depicted by the circles) and 20–25 °C (as depicted by the squares) treatments for each cream type. The central lines in each plot are the regression best fit lines and the curved lines define 99% confidence bounds. For P. acnes phage PAC1 cetomacrogol was the optimal semi-solid preparation tested. (Brown et al., 2018)

Case Study 2: Thermosensitive phage–colistin hydrogel for treating MDR A. baumannii wounds infections.

Chronic skin wounds, often infected with multidrug-resistant bacteria, are difficult to treat. This study explores a phage–antibiotic synergistic (PAS) approach combining phage vB_AbaM-IME-AB2 and colistin in thermosensitive hydrogels to combat Acinetobacter baumannii. Among several formulations, the one with 17.5% PF-127 and 3% HPMC showed the strongest antibacterial activity and long-term stability. It effectively reduced bacterial loads in both lab and ex vivo skin models, supporting its potential as a topical PAS wound dressing.

Figure 4. In vitro antibiofilm activity of the controls (PBS and blank gel) and the treatments (phage, colistin and their PAS combination in the suspension/solution and gel form). (A) Biofilm biomass reduction of bacteria in the presence of the different treatment samples. (B) Quantification of viable bacteria counts in biofilms after the various treatments. (Mukhopadhyay et al., 2024)

FAQs

References:

1. Briot T, Kolenda C, Ferry T, et al. Paving the way for phage therapy using novel drug delivery approaches. Journal of Controlled Release. 2022;347:414-424. doi:10.1016/j.jconrel.2022.05.021
2. Brown T, Petrovski S, Chan H, Angove M, Tucci J. Semi-solid and solid dosage forms for the delivery of phage therapy to epithelia. Pharmaceuticals. 2018;11(1):26. doi:10.3390/ph11010026
3. Loh B, Gondil VS, Manohar P, Khan FM, Yang H, Leptihn S. Encapsulation and delivery of therapeutic phages. Elkins CA, ed. Appl Environ Microbiol. 2021;87(5):e01979-20. doi:10.1128/AEM.01979-20
4. Mukhopadhyay S, To KKW, Liu Y, Bai C, Leung SSY. A thermosensitive hydrogel formulation of phage and colistin combination for the management of multidrug-resistant Acinetobacter baumannii wound infections. Biomater Sci. 2024;12(1):151-163. doi:10.1039/D3BM01383A