Comprehensive Study of Recent Development in Novel Drug Delivery System

Abstract

The Advanced Novel Drug Delivery System (NDDS) represents a significant evolution in pharmaceutical sciences, focusing on enhancing drug efficacy, safety, and patient compliance. Traditional drug delivery methods often suffer from poor bioavailability, rapid degradation, and systemic side effects. NDDS incorporates cutting-edge technologies such as nanoparticles, liposomes, micelles, transdermal patches, hydrogels, and polymer-based systems to improve targeted drug delivery, controlled release, and bioavailability. These systems enable precise drug localization, sustained therapeutic effects, and reduced dosing frequency, minimizing adverse effects while maximizing therapeutic outcomes. Furthermore, NDDS plays a crucial role in modern medicine, particularly in treating chronic diseases, Cancer, Neurodegenerative disorders, and also in personalized medicine. With advancements in nanotechnology, biotechnology, and smart drug carriers, NDDS continues to revolutionize the pharmaceutical industry, offering innovative, efficient, and patient-friendly treatment solutions.

Keywords

Introduction

Table No. 1 Application in various Disease

1. Cancer

Fig No. 1 Classification

Applications [6]

Fig No.2 Application

Factor Influence of NDDS [7,8]

Fig No.3 Factor Influence of NDDS

Need And Objectives of NDDS

Need

• Improved Bioavailability
• Controlled and Sustained Release
• Targeted Drug Delivery
• Reduction in Toxicity and Side Effects
• Enhanced Patient Compliance
• Overcoming Drug Resistance
• Protection of Sensitive Drugs
• Personalized Medicine

Objectives

• Enhanced Drug Bioavailability – Improving the absorption and effectiveness of drugs, ensuring they reach the target site efficiently.[9]
• Controlled and Sustained Release – Delivering drugs at a controlled rate over a prolonged period to maintain therapeutic levels and reduce dosing frequency.
• Targeted Drug Delivery – Delivering medications precisely to the impacted tissues or cells, reducing adverse effects, and improving therapeutic results. [10]
• Reduction of Drug Toxicity – Lowering the risk of adverse effects by preventing drug accumulation in non-target areas.[10]
• Improved Patient Compliance – Simplifying dosing regimens (e.g., once-daily or extended-release formulations) to enhance adherence to medication schedules.[11]
• Protection of Drugs from Degradation – Shielding sensitive drugs from enzymatic, chemical, or environmental degradation to ensure stability and efficacy. [12]
• Minimization of Drug Fluctuations in Plasma – Maintaining consistent drug levels in the bloodstream to avoid peaks and troughs that can lead to inefficacy or toxicity.
• Use of Biodegradable and Biocompatible Materials – Ensuring that medication carriers are secure, efficient, and do not result in negative bodily reactions. [13]

Evaluations:

1. Particle size and polydispersity index

The term "particle size" describes a particle's dimensions, which are frequently stated in nanometres (nm) or micrometres (µm). It is essential for figuring out a material's chemical, biological, and physical characteristics. In fields such as pharmaceuticals, nanotechnology, and material science, controlling particle size is essential for stability, bioavailability, and functionality. [14] PDI is a measure of the heterogeneity of particle sizes within a sample. It indicates how uniformly sized the particles are, with values ranging from 0 to 1:

• PDI < 0.1 → Monodisperse (uniform size distribution)
• 0.1 ≤ PDI ≤ 0.4 → Moderate polydispersity (acceptable for many applications)
• PDI > 0.4 → Highly polydisperse (broad size distribution, often unstable)

PDI is commonly used in nanoparticle formulations, especially in drug delivery systems, where uniformity in size ensures reproducibility, stability, and controlled release properties. [15]

2. Morphology

Morphology refers to the study of the structure, shape, and form of objects, including biological, geological, and material sciences. In contrast, surface topography focuses on the detailed characteristics of an object's surface, including roughness, texture, and microstructures. [16]

3. Thermo-analytical methods

Thermo-analytical methods are techniques used to study the physical and chemical properties of materials as they change with temperature. These methods are widely used in materials science, chemistry, pharmaceuticals, and polymer industries to analyse phase transitions, decomposition, and other thermal properties. [17]

Common Thermo-Analytical Methods

1. Thermogravimetric Analysis (TGA)
   • Determines how a sample's mass changes over time or as a function of temperature in a controlled environment.
   • Used for studying thermal stability, decomposition, oxidation, and moisture content.
2. Differential Scanning Calorimetry (DSC)
   • Measures the heat flow associated with phase transitions such as melting, crystallization, and glass transition.
   • Useful for determining heat capacity, purity, and reaction enthalpy.
3. Differential Thermal Analysis (DTA)
   • As the sample and an inert reference are heated, the temperature difference between them is recorded.
   • Identifies exothermic and endothermic reactions like crystallization, decomposition, and phase transitions.
4. Thermomechanical Analysis (TMA)
   • Measures changes in physical properties (e.g., expansion, softening) under controlled temperature and force.
   • Useful for studying the thermal expansion coefficient and mechanical behaviour of materials.
5. Dynamic Mechanical Analysis (DMA)
   • Examines the viscoelastic behaviour of materials by applying oscillating force while varying temperature.
   • Used for studying mechanical properties like modulus, damping, and transition temperatures.
6. Evolved Gas Analysis (EGA)
   • Identifies gases released during thermal decomposition using techniques like mass spectrometry (MS) or Fourier-transform infrared spectroscopy (FTIR).
   • Useful in polymer degradation, combustion studies, and environmental analysis.

4. Infra-Red spectroscopy

An analytical method called infrared (IR) spectroscopy uses the way that chemicals absorb infrared light to identify and investigate them. Chemistry, medicine, materials science, and forensic analysis all make extensive use of it. [18]

5. Loading efficiency and production yield

1. Loading Efficiency

This refers to how effectively materials, products, or goods are loaded into a system—whether a machine, vehicle, or production line. It is often measured in terms of:[19]

• Space Utilization: Maximizing capacity in transport or storage.
• Time Efficiency: Reducing the time taken to load materials.
• Labor Efficiency: Minimizing manual effort and optimizing automation.
• Material Handling Efficiency: Reducing waste and damage during loading.

2. Production Yield

This is the measure of how many usable products are successfully produced compared to the total input. It is calculated as:[20] Yield is equal to the sum of the good units produced. ×100 With \left (\frac {\text Good Units Produced} {\text {Total Units Produced}} \right) \times, \ text {Yield}= One hundred (Total Units Produced Good Units Produced) ×100 = Yield

Factors affecting production yield include:

• Raw Material Quality: Better inputs lead to fewer defects.
• Machine Efficiency: Well-maintained machines reduce defects.
• Process Optimization: Reducing rework and waste improves yield.
• Quality Control: Strict inspections ensure fewer defective products.

6. Solubility studies

Solubility studies focus on determining how much of a substance (solute) can dissolve in a given solvent under specific conditions. These studies are crucial in various fields, including pharmaceuticals, chemistry, environmental science, and material science.[21]

7. Zeta potential

The electrostatic potential at a particle's sliding plane in a liquid medium is known as the zeta potential. It is a crucial sign of colloidal dispersions' stability. Strong particle repulsion, which inhibits aggregation and ensures stability, is indicated by a high absolute zeta potential, either positive or negative. Weak repulsion is indicated by a low zeta potential, which can result in flocculation or coagulation.[22]

Key Aspects of Zeta Potential:

• Measured in millivolts (mV).
• Positive or negative values indicate the charge of the particles.
• Threshold for stability:
  • ±30 mV or higher → Stable dispersion.
  • Between ±10 to ±30 mV → Moderately stable.
  • Less than ±10 mV → Likely to aggregate.

8. Dissolution Test

In the pharmaceutical industry, a dissolution test is a laboratory technique used to quantify the rate at which an active pharmaceutical ingredient (API) dissolves into a dissolving medium from a dosage form (such as tablets or capsules). It is an essential test for guaranteeing the consistency, quality, and bioavailability of drugs.[23]

Justification

The need for Novel Drug Delivery Systems (NDDS) arises from the growing demand for enhanced efficacy, safety, patient adherence, and precision in medical treatments. Conventional drug delivery methods often suffer from limitations such as poor bioavailability, rapid degradation, systemic side effects, and non-specific targeting, which NDDS seeks to address.

1. Improved Therapeutic Effectiveness
   • NDDS enables controlled and sustained drug release, ensuring consistent therapeutic levels over extended periods.
   • Enhanced bioavailability reduces required dosages, minimizing toxicity while optimizing treatment outcomes.
2. Targeted Drug Delivery
   • Nanotechnology-based carriers (e.g., liposomes, nanoparticles, and micelles) facilitate site-specific drug delivery, enhancing medication accumulation at the target site and decreasing systemic side effects.
   • In cancer treatment, targeted drug delivery minimizes damage to healthy tissues.
3. Enhanced Patient Compliance and Convenience
   • Lower dosing frequency (e.g., once-daily formulations instead of multiple doses) improves adherence.
   • Non-invasive delivery options like transdermal patches, nasal sprays, and oral thin films offer a more comfortable alternative to injections.
4. Overcoming Physiological Barriers
   • Blood-brain barrier (BBB) penetration: Advanced NDDS formulations enable efficient drug delivery for neurological conditions.
   • Gastrointestinal stability: Enteric-coated and nano-formulated drugs protect against acidic degradation in the digestive tract.
5. Advancements in Personalized Medicine
   • NDDS enables precision medicine by tailoring drug delivery based on individual genetics, disease characteristics, and metabolism.
6. Economic and Industrial Advantages
   • Fewer hospital visits and reduced adverse effects contribute to lower healthcare costs.
   • Pharmaceutical companies gain extended patent protection for reformulated drugs, promoting innovation and market sustainability.

Challenges of Novel Drug Delivery Systems (NDDS)

• Problems and solutions related to the distribution of poorly soluble medications.
• Innovative methods for administering medications that are poorly soluble.
• Overcoming obstacles to bioavailability for clinical candidates with poor solubility.
• Justification for formulation design for chemicals with low solubility.
• Overcoming obstacles in the delivery of protein drugs.
• Difficulties with medicine delivery in children and the elderly.
• Overcoming the drug's addictive nature.

Future Aspects of Advanced NDDS

The future of Advanced Novel Drug Delivery Systems (NDDS) is highly promising, with emerging technologies transforming how drugs are administered, absorbed, and targeted within the body. Key advancements include:[24]

1. Nanotechnology-Driven Drug Delivery
   • Nanoparticles & Liposomes: Enhance bioavailability, ensure targeted delivery, and minimize side effects.
   • Polymeric Nanoparticles: Enable sustained and controlled drug release.
   • Dendrimers & Micelles: Provide high drug-loading capacity with precise targeting.
2. Smart & Stimuli-Responsive Systems
   • pH-Sensitive & Temperature-Responsive Carriers: Release drugs based on physiological conditions.
   • Magnetic & Ultrasound-Activated Systems: Offer externally controlled drug release mechanisms.
3. Gene & Cell Therapy Delivery
   • CRISPR-Based Gene Delivery: Advances in treating genetic disorders.
   • Viral & Non-Viral Vectors: Enhance targeted and safer gene therapy approaches.
4. 3D Printing for Personalized Medicine
   • Customized Dosage Forms: Enables patient-specific drug release profiles.
   • Multi-Layered Drug Release: Allows the delivery of multiple drugs in a single dose.
5. Artificial Intelligence (AI) & Machine Learning
   • Predictive Modelling: Aids in designing optimized drug formulations.
   • AI-Driven Drug Screening: Accelerates discovery and refinement of drug delivery systems.
6. Microneedle Patches & Wearable Devices
   • Painless & Self-Administered Drug Delivery: Ideal for biologics, insulin, and vaccines.
   • Smart Patches: Enable real-time monitoring and automated drug release.
7. Bioelectronic Medicine & Implantable Devices
   • Microchip-Controlled Drug Release: Allows wireless-controlled dosing.
   • Brain-Computer Interfaces: Facilitate targeted drug release for neurological disorders.
8. Extracellular Vesicle-Based Therapy
   • Exosome-driven drug Delivery: Utilizes natural carriers for precision medicine.
9. Hydrogel-Based Carriers
   • Biodegradable & Injectable Hydrogels: Support long-term and sustained drug delivery.
10. Theragnostic: Integrated Therapy & Diagnostics

• Real-Time Monitoring & Treatment: Leverages nanoparticles for both diagnostics and therapy.

The convergence of nanotechnology, AI, 3D printing, and biotechnology is set to revolutionize NDDS, ensuring treatments are more efficient, targeted, and personalized.

CONCLUSION

Drug therapy is becoming more efficient, targeted, and patient-friendly thanks to the Advanced Novel Drug Delivery System (NDDS), which is revolutionizing pharmaceutical sciences. Innovations in nanotechnology, polymer science, and controlled-release formulations are paving the way for safer, more efficient, and personalized treatments. While challenges remain, continuous research in biotechnology and smart drug carriers promises a future where drug delivery is precise, non-invasive, and highly efficient. The future of medicine lies in smarter, more advanced drug delivery systems, ensuring better healthcare for all. The conclusion of Advanced Novel Drug Delivery Systems (NDDS) emphasizes the transformative impact of these technologies in modern pharmaceutical sciences. NDDS enhances drug efficacy, improves patient compliance, and minimizes side effects through targeted and controlled release mechanisms. Various innovative systems, such as nanoparticles, liposomes, dendrimers, and micelles, have revolutionized drug formulation and delivery, ensuring better bioavailability and therapeutic outcomes. Despite significant progress, challenges remain, including scalability, regulatory approvals, and potential toxicity concerns. Nonetheless, ongoing studies and developments in the fields of nanotechnology, biotechnology, and material sciences portend a time when NDDS will be essential to the treatment of complicated illnesses and personalized medicine.

REFERENCES

1. 1. 1. 1. Alharbi WS, Almughem FA, Almehmady AM, et al. Phytosomes as a rising nanotechnology platform for delivering bioactive phytochemicals topically. Pharmaceutics,2021;13:1475. https://doi.org/10.3390/pharmaceutics13091475
         2. A comprehensive review of innovative drug delivery systems. JETIR, September 2020, Vol. 7, Issue 9. www.jetir.org (ISSN-2349-5162)
         3. Borase VA, Kapadnis RS, Chaudhary AY, Bachhav RS. An overview of novel drug delivery systems. IJRAR, January 2021, Vol. 8, Issue 1. www.ijrar.org (E-ISSN-2348-1269)
         4. Danaei M, Dehghankhold M, Atari S, Hasanzadeh Devarni F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Influence of particle size and polydispersity index on the clinical application of lipid-based nanocarriers. Pharmaceutics, 2018; 10(2): 57.
         5. Sharma N, Purwar N, Gupta PC. Microspheres as controlled drug delivery carriers: A review. Int. J. Pharm. Sci. Res., 2015; 6(11): 4579.
         6. Kumari P, Shankar C, Mishra B. “The Indian Pharmacist,” Vol. III, No. 24, June 2004, pp. 7-16.
         7. Lee VHL, Robinson JR. J. Pharm. Sci., 1979; 68: 673.
         8. Banker GBS, Rodes CT. "Modern Pharmacist," 2nd edition, Vol. 40, Marcel Dekker, New York, 1979, pp. 263-273, 283, 286-287, 299-311.
         9. Lemberger AP. "A Handbook of Non-Prescription Drugs," American Pharmaceutical Association, Washington, 1973, p. 161.
         10. Wilkes GL, Brown IA, Wilnauer RH. CRC Crit. Rev. Bioeng., August 1973, p. 453.
         11. Katz MA, Cheng CH, Nacht S. Methods and formulations for topical benzoyl peroxide delivery. US Patent No. 5,879,716 (March 9, 1999).
         12. Ting WW, Vest CD, Sontheimer RD. A review of conventional and new approaches to enhance local therapeutic permeability across the stratum corneum. Int. J. Dermatol., 2004; 43(7): 538-547.
         13. Schafer-Korting M, Korting HC, Ponce Poschl E. Liposomal tretinoin for treating uncomplicated acne vulgaris. Clin. Investig., 1994; 72(12): 1086-1091.
         14. Arunachalam A. Asian J. Pharm. Anal. Med. Chem.
         15. Kaur D, Kumar S. Niosomes: Current status and future prospects. J. Drug Deliv. Ther., 2018; 8(5): 35-41.
         16. Pawar MS, Pandya M, Mishra AK. Formulation and optimization of Dugdhavardhan granules, a herbal galactagogue. Int. J. Pharm. Res., 2021; 13(2).
         17. Nandi K, Sen DJ, Patra F, Nandy B, Bera K, Mahanti B. Evaluating the relationship between the angle of repose, Carr index, and Hausner ratio. World J. Pharm. Pharm. Sci., 2020; 9: 1565-1579.
         18. Kaleem MA, Alam MZ, Khan M, Jaffery SH, Rashid B. Experimental analysis of Hausner Ratio and Carr Index accuracy in additive manufacturing powders. Metal Powder Rep., 2021; 76: S50-54.
         19. Zou T, Lu W, Mezhuev Y, Lan M, Li L, Liu F, Cai T, Wu X, Cai Y. Nanoparticle drug delivery systems responsive to the breast cancer microenvironment: A review. Eur. J. Pharm. Biopharm., 2021; 166: 30-43.
         20. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery vehicles. J. Control. Release, 2001; 70: 1-20.
         21. Mueller RH, Wallis KH. Surface modification of biodegradable injectable nanoparticles with poloxamer and poloxamine polymers. Int. J. Pharm., 1993; 89: 25-31.
         22. Li N, Wang J, Yang X, Li L. Novel nanogels for poorly soluble anticancer drug delivery. Colloids Surf. B Biointerfaces, 2011; 83(2): 237-244.
         23. Ta HT, Dass CR, Larson I, Choong PF, Dunstan DE. Chitosan–dipotassium orthophosphate hydrogel for doxorubicin delivery in osteosarcoma treatment. Biomaterials, 2009; 30(21): 3605-3613.
         24. Kaur D, Kumar S. Niosomes: Current trends and future perspectives. J. Drug Deliv. Ther., 2018; 8(5): 35-41.