Pharmaceutical Research Applications of Carbohydrates and Polysaccharides
Dr. Sai Sandeep Mannimala, Global Product ManagerMerck
Carbohydrates are increasingly used in pharmaceutical research, evolving from traditional excipients to versatile functional materials capable of addressing diverse formulation challenges. Their structural diversity, biocompatibility, functional tunability, and regulatory acceptance make them essential for modern therapeutic development, from improving solubility and stability to enabling controlled release.1 This paper summarizes current research and application insights across major carbohydrate classes, supporting formulation scientists, biotechnologists, and drug delivery specialists in the design of robust and effective dosage forms.
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Introduction to Carbohydrates in Therapeutics
Carbohydrates are now recognized as active functional components in drug delivery rather than just passive excipients. Recent studies demonstrate that carbohydrate systems can achieve outcomes difficult to replicate with synthetic alternatives, such as FDA-approved nanoparticle therapeutics, self-healing wound care hydrogels, and precision-targeted drug delivery with minimal side effects. With the mounting complexity of APIs, the rise of biologics, and the demand for advanced delivery systems, carbohydrate-based excipients and carriers are solving critical challenges in formulation across a wide range of applications.2
Why Carbohydrates Excel in Modern Drug Delivery
Carbohydrates have distinctive properties that not only enhance the efficacy of pharmaceutical formulations but also address critical challenges in targeted therapy. By leveraging their structural diversity and biocompatibility, carbohydrates offer innovative solutions that align with the evolving needs of modern medicine.
Unique Structural Advantages for Drug Delivery
Carbohydrates possess unique structural features that directly translate to pharmaceutical functionality. Their high density of functional groups, such as hydroxyl, carboxyl, amine, and sulfate moieties, provides multiple sites for precise chemical modification and intermolecular interactions. This functional diversity enables researchers to fine-tune critical properties like solubility, mucoadhesion, and release kinetics with remarkable precision.1
The stereochemical complexity of carbohydrates offers another decisive advantage. Unlike synthetic polymers with relatively simple backbone structures, carbohydrates adopt complex three-dimensional conformations that enable specific biological recognition events.3 This property proves invaluable in targeted drug delivery, where molecular recognition between carbohydrate ligands and cellular receptors can direct therapeutics to specific tissues with 5 to 15-fold improved selectivity over non-targeted systems.4,5
Biocompatibility and Regulatory Benefits
The safety profile of carbohydrate excipients stems from their natural occurrence and established metabolic pathways. Unlike synthetic polymers that may accumulate in tissues, most carbohydrates are readily metabolized through endogenous enzymatic processes or excreted unchanged. This inherent biocompatibility translates to streamlined regulatory pathways and reduced safety testing requirements. Beyond simple safety considerations, many carbohydrates possess intrinsic biological activities that enhance therapeutic outcomes.6
Cost-Effectiveness and Sustainability
Unlike petroleum-derived synthetic polymers subject to volatile pricing, most carbohydrate raw materials benefit from stable agricultural and marine sources.7 Market reports indicate the global pharmaceutical excipients market is growing at a compound annual growth rate of 6–8%, driven significantly by the rising uptake of biologic therapeutics and a shift towards natural, sustainable excipients such as polysaccharides and carbohydrate-based stabilizers.8,9
Carbohydrate Types and Pharmaceutical Applications
Carbohydrates serve diverse functions in therapeutic research, from excipients to specialized delivery vehicles. Many are employed in carbohydrate matrices that provide controlled release, stabilization, and targeted delivery functions.
Cellulose Derivatives: Controlled Release and Matrix Systems
Hydroxypropyl methylcellulose (HPMC) remains the gold standard for oral controlled-release research due to its predictable gel-forming behavior and excellent safety profile. Different viscosity grades (4,000-100,000 cP) enable precise control over release duration, with higher viscosity grades providing more sustained release through enhanced gel layer formation. Recent research reveals that molecular weight distribution significantly influences gel layer properties, with broader distributions providing more consistent zero-order release profiles.10
Microcrystalline cellulose (MCC) brings dual functions as both binder and disintegrant, depending on grade selection and processing conditions. Its high surface area and excellent compaction properties make it ideal for direct compression formulations, while its chemical inertness ensures compatibility with most active ingredients.11
Ethyl cellulose delivers hydrophobic matrix properties essential for moisture-sensitive drugs and extended-release applications requiring minimal water uptake. Its film-forming capabilities make it valuable for coating applications where controlled permeability is required.12
Starch and derivatives serve as cost-effective alternatives for binding and disintegration applications. Amylopectin, the branched component of starch, offers excellent binding properties, while dextrin (partially hydrolyzed starch) offers improved solubility for specialized applications.13
Cellulose, Starch and Their Derivatives
Chitosan and Marine Polysaccharides: Carbohydrate Specialized Delivery Systems
Chitosan's cationic nature enables unique applications in mucoadhesive delivery and cellular uptake enhancement. The degree of deacetylation (typically 75-95%) directly influences both solubility and biological activity, with higher deacetylation providing stronger mucoadhesion but reduced solubility in neutral pH environments. Chemical modifications like quaternized chitosans maintain positive charge across wider pH ranges, while thiolated chitosans form disulfide bonds that enhance mucoadhesion duration.14
Hyaluronan (hyaluronic acid) provides exceptional biocompatibility and tissue integration properties, making it invaluable for ophthalmic, injectable, and wound care applications. Its viscoelastic properties and ability to bind large amounts of water create ideal conditions for sustained drug release and tissue regeneration.15,16
Sodium alginate offers unique gelation properties through calcium-induced crosslinking. The guluronic to mannuronic acid ratio (G/M ratio) determines gel characteristics: high-G alginates form strong, brittle gels suitable for rapid release applications, while high-M alginates create flexible gels ideal for sustained release.17
Carrageenan, available in three main types (kappa, iota, and lambda), provides thermoreversible gelling with tunable mechanical properties. This diversity enables precise property matching for specific applications.18
Heparin and derivatives offer unique anticoagulant properties combined with drug delivery capabilities. Beyond their therapeutic anticoagulant effects, heparin-based systems can enhance drug permeation and provide targeted delivery to specific tissues through receptor-mediated mechanisms.19
Fucoidan, a sulfated polysaccharide from brown seaweed, demonstrates promising immunomodulatory and anti-inflammatory properties. Research indicates potential applications in cancer therapy and immune system modulation, though commercial development remains in early stages.20
Chitosan and Marine Polysaccharides
Cyclodextrins and Solubility Enhancers: Bioavailability Optimization
Cyclodextrins operate through molecular encapsulation, sequestering hydrophobic drug molecules within their cavities while maintaining aqueous solubility. β-cyclodextrin provides excellent solubilization for many drugs, with its 6-8 Å diameter accommodating most pharmaceutical compounds.21
Modified cyclodextrin derivatives offer enhanced pharmaceutical properties. For instance, carboxymethyl-β-cyclodextrin and methyl-β-cyclodextrin provide improved solubility and stability while enabling sustained-release formulations for poorly soluble drugs.22,23
Mannose serves dual roles as both a targeting ligand and solubility enhancer. Its specific binding to mannose receptors on antigen-presenting cells enables targeted delivery for vaccine and immunotherapy applications.24,25
Meglumine serves as a pharmaceutically acceptable base for forming salts with acidic drugs, improving solubility and stability while maintaining excellent biocompatibility for poorly soluble drugs.26
Cyclodextrins and Solubility Enhancers
Dextrans and Derivatives: Advanced Bioconjugation Platforms
Dextran represents one of the most successful carbohydrate platforms for pharmaceutical applications, with multiple FDA-approved products demonstrating its clinical viability. This α-1,6-linked glucose polymer offers exceptional biocompatibility, controlled biodegradation, and versatile chemical modification possibilities.27
The molecular weight range spans from 1 kDa to 2,000 kDa, with each size range offering distinct pharmacokinetic and functional advantages in drug delivery applications. Low molecular weight dextrans (1-10 kDa) provide rapid renal clearance and minimal immunogenicity, while medium molecular weight dextrans (10-100 kDa) offer optimal balance between circulation time and clearance. High molecular weight dextrans (>100 kDa) serve as plasma expanders and provide extended circulation times for drug conjugates.28
Dextran’s versatility multiplies when chemically modified:
- Carboxymethyl dextran introduces negative charges for ionic interactions with cationic drugs29
- Diethylaminoethyl (DEAE) dextran provides cationic functionality that enhances cellular uptake and enables complexation with nucleic acids for gene delivery applications30
- Dextran sulfate adds anticoagulant properties and doubles as a nanoparticle precursor31
- Iron-dextran complexes represent the most clinically successful dextran application, with multiple approved products for treating iron deficiency anemia32
Dextrans and its Derivatives
Natural Gums and Sugar Alcohols: Rheology and Specialized Applications
Xanthan gum forms pseudoplastic (shear-thinning) solutions that remain viscous at rest but flow easily under stress, making it ideal for stable and user-friendly drug delivery systems like gels, emulsions, and injectables.33
Guar gum, a galactomannan polysaccharide, is valued for its strong thickening and binding capabilities at low concentrations. It has been extensively explored for the preparation of hydrogels, nanoparticles, nanocomposites, and bioactive scaffolds.34
Gum arabic (acacia gum) provides superior emulsification properties combined with excellent biocompatibility.35 Locust bean gum demonstrates synergistic gelling behavior when combined with other gums, particularly xanthan and carrageenan.36
Pectin offers pH-responsive gelling behavior, forming strong gels in acidic conditions while remaining fluid at neutral pH. This property enables gastric-resistant formulations and colon-targeted delivery systems.37
Sugar alcohols serve specialized functions: Mannitol functions as an osmotic agent, bulking agent, and stabilizer with low hygroscopicity. Sorbitol provides excellent plasticizing properties for film coatings. Lactitol offers advantages through its lower caloric content and reduced laxative effects. Xylitol demonstrates unique antimicrobial properties, particularly against oral bacteria.38
Natural Gums and Sugar Alcohols
Specialized and Emerging Carbohydrates
β-D-glucan represents an emerging class of immunomodulatory carbohydrates with significant potential in vaccine adjuvants and cancer immunotherapy. These polysaccharides activate immune cells through specific receptor binding, triggering innate immune responses39.
Inulin, a fructan polymer, offers prebiotic benefits combined with drug delivery capabilities. Its selective fermentation by beneficial gut bacteria enables colon-targeted delivery while providing additional therapeutic benefits through microbiome modulation40.
Lactose remains a cornerstone excipient for inhalation formulations due to its excellent flow properties and established safety profile for pulmonary delivery41. Lactulose offers unique prebiotic properties combined with laxative effects, enabling dual-action formulations for gastrointestinal applications41.
Trehalose has emerged as a premium stabilizer for biologics and vaccines, providing superior protein protection during freeze-drying and storage compared to traditional stabilizers. Its non-reducing nature prevents Maillard reactions that can degrade sensitive proteins42.
Sucrose remains one of the most versatile pharmaceutical excipients, serving as a sweetener, bulking agent, and stabilizer across multiple dosage forms. Its critical role in biologics stabilization involves forming hydrogen bonds with proteins during dehydration and maintaining structural integrity during freeze-drying processes43.
Inositol serves specialized roles in neurological and psychiatric formulations, where its vitamin-like properties provide therapeutic benefits beyond simple excipient function. Research demonstrates its utility in sustained-release formulations for mood disorders44. Glycogen offers unique properties as a highly branched glucose polymer with potential applications in sustained-release formulations45.
Acarbose represents a unique example where the carbohydrate itself serves as the active pharmaceutical ingredient, inhibiting α-glucosidase enzymes for diabetes research46. Sodium gluconate serves dual roles as a chelating agent and pH buffer in pharmaceutical formulations.
Specialized and Emerging Carbohydrates
Conclusion
Carbohydrates have advanced from simple binders and fillers to multifunctional excipients that underpin modern pharmaceutical formulations. Their structural versatility, safety, and ability to fine-tune solubility, release, and stability continue to expand their role across dosage forms. As research progresses, careful selection of carbohydrate materials will remain essential for developing reproducible, effective, and sustainable therapeutic products.
Explore our full portfolio of carbohydrate products to support advanced formulation studies.
All products are for research use only.
References
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