INTRODUCTION:

Therapeutic delivery methods have been transformed by the development of nanotechnology, which has produced innovative nano-scale formulations with the goal of increasing therapeutic efficacy. Nanocrystals, colloidal dispersions of drug particles at the nanoscale stabilized by surfactants or polymers, are one example of such a system¹. Elan Drug Technologies' Rapamune product marked the launch of nanocrystals into the market in 2000². Since then, the potential to improve bioavailability and permeability without solubilizing with organic solvents has made nanocrystal formulations for poorly soluble medicines more attractive³. The size range of nanocrystals is 10-400 nm. The Ostwald-Freundlich equation, states that decreasing particle size to the nanoscale increases the surface area to volume ratio and enhances saturation solubility⁴.

Received on 26.03.2024 Revised on 21.10.2024

Accepted on 05.02.2025 Published on 13.01.2026

Available online from January 17, 2026

Research J. Pharmacy and Technology. 2026;19(1):452-458.

DOI: 10.52711/0974-360X.2026.00066

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

With decreasing particle sizes, the Noyes-Whitney equation also predicts a rise in dissolving velocity⁵. Due to these characteristics, weakly water-soluble medications (class II and IV in the Biopharmaceutics Classification System) with low bioavailability are best delivered by means of nanocrystals⁶.The primary issue with standard formulations, especially for water-soluble medicines, appears to be unpredictable bioavailability. Modification of chemical and physical processes to reduce particle size and increase (better) solubility. To boost the drug's bioavailability and rate of dissolution, micronization to nanonization is required. This comprises innovative ideas and tactics based on nanotechnology for all physicochemical and stability issues associated with nanostructures. Different type of nanotherapeutic formulation is shown in (figure 1).

Figure 1: Different types of nanotherapeutics formulation

In addition to improving solubility, nanocrystals offer benefits such as improved adhesiveness, ease of synthesis, and adaptability in delivery methods⁷. A great deal of research has been done on nanocrystal administration via oral, pulmonary, ophthalmic, and parenteral routes⁸. Their use in transdermal and topical administration has drawn attention lately. Direct access to the site of action and prevention of gastrointestinal adverse effects and first-pass metabolism are two benefits of topical application⁹. Non-invasive sustained medication release into the systemic circulation is made possible by transdermal administration. Nonetheless, most medications can only penetrate the skin so far due to their barrier role¹⁰. This restriction can be removed by nanocrystals, allowing drugs to pass through the skin more easily.The goal of this review is to present a thorough summary of the most recent studies on nanocrystal technology for transdermal and topical medication administration. The preparation, stabilization, and characterisation techniques for nanocrystals are covered in the first section. The mechanisms by which nanocrystals promote skin penetration are explained in the following section. A critical analysis of the various topical and transdermal delivery routes investigated for nanocrystal compositions follows below. A review is also conducted on the advancement of nanocrystal goods into clinical trials and the market. Finally, the importance of nanocrystals in topical medication delivery is reviewed, along with present and future obstacles and opportunities.

Advantages of Nanocrystals in Drug Delivery¹⁰:

1. Poorly water-soluble compounds can be formulated as nanocrystals, which can improve their dissolution rates and its bioavailability.

2. Large Surface Area nanocrystals enormous surface area enhances fast drug release and penetration into the skin.

3. Nanocrystal stability provides a protective environment for sensitive substances, preventing degradation and extending shelf life.

4. Targeted Distribution, Because of their microscopic size, they can precisely target certain skin layers or lesions.

Disadvantages:

1. Products need to be handled and transported very carefully.

2. It is difficult to adjust dosage form correctly and shows Physical stability.

METHOD OF PREPARATIONS OF NANOCRYSTALS:

Top-down procedures such as media milling and high-pressure homogenization convert coarse drug microparticles to nano-sized crystals. Media milling is combining medication suspensions with milling media and grinding for hours to reach the appropriate particle size. High-pressure homogenization breaks down microparticles using shear, impact, and cavitation forces in piston-gap homogenizers. Microfluidic homogenizers use high-speed suction through microchannels to reduce particle size^11,12. Bottom-up approaches produce nanocrystals from solubilized molecules using techniques such as antisolvent precipitation, supercritical fluid precipitation, hot melt extrusion, spray drying, spray freeze drying, and ultrasonication. Stabilizers such as cellulosic, polysaccharides, polymers, and surfactants adsorb onto the nanocrystal surface to provide stability during formulation¹³.By strengthening drug partitioning into the skin, producing an occlusive film on the skin's surface, and enhancing saturation solubility in the stratum corneum, nanocrystals improve topical and transdermal drug delivery. Higher medication concentrations in the underlying skin layers result from this, improving both local and systemic effects. The marketed formulations of nanocrystal formulations shown in (Table1).

Top-Down Technique:

Media milling:

The most popular top-down fabrication technique is this one. Using beads or pearls as grinding media, the medication microparticles are mechanically attrition-tested in a milling chamber. The particles are broken down into nanoscale crystals by strong shear pressures. The final crystal size can be controlled by optimizing parameters such as milling time, speed, and bead material/size. Drugs like Amphotericin B, Econazole, and Dexamethasone have all been subjected to media grinding^14-16.

High-pressure homogenization:

High-pressure homogenization produces drug nanocrystals by processing macro suspensions with a high-energy approach that involves particles passing through a tight gap at high speeds. Cavitation and crystal collision energy convert drug particles into nanosized crystals, resulting in nanosuspensions. This method includes pushing a drug suspension at high pressure through a small hole, using cavitation, turbulence, and shear forces to reduce particle size. Common equipment includes microfluidizers and piston-gap homogenizers, which require numerous cycles to produce homogeneous nanocrystals. High-pressure homogenization has successfully produced nanocrystals of medications such as quercetin, hydrocortisone, and retinoic acid^14,15.

Sonication:

Sonication uses ultrasound energy to break apart microparticle aggregates and drug crystals suspended in liquid. The imploding cavitation bubbles and strong hydrodynamic shear forces of sonication result in smaller nanosized crystals. Sonication parameters like amplitude, cycle, and duration can control the particle size. Sonication has been used to prepare nanocrystals of minoxidil, finasteride, and other topical drugs^14,15.

Bottom-Up technique:

Precipitation: This process involves precipitating medication nanocrystals from a supersaturated solution. Supercritical fluids, temperature or pH changes, antisolvent addition, and other methods are employed to create supersaturation and precipitation. The ultimate size and growth of drug crystals are determined by the rate of supersaturation formation. Econazole nitrate and clobetasol propionate nanocrystals have been prepared for topical administration through the use of precipitation^14-16.

Hot-Melt Extrusion: The medication is first dissolved in a heated polymer melt before being extruded. The medication recrystallizes into nanoscale crystals embedded in the matrix when the melt cools and solidifies. Crystal size is influenced by variables such as temperature, screw design, and extrusion rate. The formulation of topical nano emulsions and nanogels containing medication nanocrystals has been studied in relation to hot melt extrusion^14-16.

Spray Drying: This method involves dissolving the medication in an organic solvent before atomizing it into a fine-droplet spray. The drug precipitates and crystallizes into nanoparticles that are collected as the solvent quickly evaporates from the spray. Crystal size can be altered by spray drying parameters such as feed rate, inlet temperature, and atomization pressure. Topical medication delivery using spray-dried nanocrystal microparticles has been created^14-16.

Supercritical fluid technology: Bottom-up technologies, such as supercritical fluid engineering, show promise for creating accurate nanocrystals, but they must be optimized and stabilized. The features of the SCF method include fast solvent removal, the use of supercritical fluid qualities for speedy micro-mixing, and the RESS process for drug precipitation. Dangerous solvents, greater surfactant ratios, the risk of nucleation overgrowth, and the possibility of creating amorphous forms are all challenges^14-17.

Characterization Of Nanocrystals for Drug Delivery

Size Distribution and Particle Size: The size of nanocrystals and the polydispersity index have an impact on medication penetration through the skin. Size is determined using methods such as dynamic light scattering (DLS), laser diffraction (LD), and nanoparticle tracking analysis (NTA)^14-19. Combining approaches is frequent due to limitations, DLS struggles with extremely polydisperse systems, and LD is less accurate below 1 μm in diameter.

Surface Charge (Zeta Potential): The stability of nanocrystals in the dispersion is influenced by the surface charge. An electric field is applied to a solution containing the particles in order to measure the zeta potential. Greater stability and larger repulsive forces between particles are indicated by more positive or negative values. Methods such as electrophoretic light scattering are used to measure it¹⁹.

Morphology: Particle morphology, including as shape and surface topography, can be seen using imaging techniques like atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Samples that are frozen hydrated can be imaged using cryo-TEM^18-20.

Crystallinity: The crystalline condition is ascertained and the chemical integrity is verified using X-ray diffraction analysis. Information on the melting point, recrystallization events, and solid-state characteristics can be obtained using differential scanning calorimetry^20-22.

Drug Release (in vitro): The nanocrystal formulation's release kinetics shed light on aspects such as burst release, sustained release behaviour, and dissolution enhancement compared to plain medication. Dialysis membranes or Franz diffusion cells are used to assess in vitro release²³.

Properties of Nanocrystals:

Enhanced Dissolution Velocity: Nanocrystals have a significantly higher surface area than larger particles, increasing the rate of disintegration. This property is critical for increasing the bioavailability of poorly soluble drugs since it accelerates the drug's rate of dissolution in the body. As a result, nanocrystals have a larger surface area, which leads to faster disintegration²⁴.

Increased Saturation Solubility: Nanocrystals are more soluble in saturated solutions than micrometer-sized particles. This suggests that more of the medication can dissolve in a given solvent when utilizing nanocrystals, potentially enhancing the efficacy and efficiency of drug delivery²⁵.

Adhesiveness: The gastrointestinal and biological mucosa are naturally drawn to nanocrystals. Because it allows for more pharmaceutical interaction and absorption at the site of action, adhesiveness is beneficial for drug delivery and may boost therapeutic benefits²⁶.

Zeta Potential: The physical stability of nanocrystals is largely determined by their zeta potential. Both the stabilizing agent and the medicinal ingredient have an effect on it. To work in drug delivery systems, nanocrystals must maintain electrostatic stability at a specific zeta potential²⁷.

Crystal/Structural Morphology: X-Ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC) are used to evaluate nanocrystals amorphous shape and crystal structure. Understanding crystal form is crucial when assessing the efficacy and stability of nanocrystals in medicine compositions²⁸.

Stability Study: Nanocrystals are studied for long-term chemical and physical stability. To ensure the dependability and efficacy of nanocrystal formulations, characteristics such as degradation, sedimentation, agglomeration, and crystal formation are monitored. As a result, stability studies on nanocrystals are conducted to determine their chemical and physical stability over time²⁹.

Versatility in Dosage Forms: Nanocrystals, which are versatile in terms of size and surface properties, can be employed in a range of dosage forms such as tablets, pellets, capsules, and dry formulations. Because of their versatility, drug delivery techniques can be tailored to the specific needs of each prescription. Nano-crystals can be easily converted into a variety of dosage forms, including pills, pellets, and capsules³⁰.

Surface Tailoring: Nano-crystals allow for drug delivery at particular sites. Nanocrystals change their surface properties, allowing for site-specific medicine administration. Using this feature, drugs can be delivered to specific tissues or organs, boosting therapeutic efficacy and lowering side effects³¹.

Pharmaceutical Application of Advanced Statistical Concepts:

Many aspects of drug development and pharmaceutical research rely heavily on advanced statistical concepts. The most significant characteristics of drug nanocrystals include enhanced saturation solubility and accelerated dissolution velocity. Drug nanocrystals exhibit superior absorption behaviour compared to micronized drugs shown in (figure 2).

Figure 2. Drug nanocrystals exhibit superior absorption behavior compared to micronized drugs.

Clinical Trials Design:

To ensure the reliability of research procedures, randomization, and blinding techniques, advanced statistical tools are used during clinical trial design and analysis. Bayesian statistics and adaptive design are two strategies for optimizing trial efficiency and decision-making³².

Analysis of Drug Efficacy and Safety:

Statistical models are used to analyze clinical trial data on drug efficacy and safety. Treatment effects and adverse events are assessed using approaches such as mixed-effects models, logistic regression, and survival analysis³³.

Pharmacokinetics and Pharmacodynamics (PK/PD):

To better understand drug absorption, distribution, metabolism, and excretion, PK/PD data is exposed to advanced statistical modeling. Drug reactions can be anticipated and dosage regimes adjusted using population pharmacokinetics and pharmacodynamics modelling³⁴.

Quality Control and Process Optimization:

Pharmaceutical producers utilize statistical process control (SPC) to monitor and improve product quality. Design of experiments (DOE) is used to identify key process parameters and optimize formulation procedures³⁵.

Studies on Bioequivalence and Bioavailability:

Statistical analysis is essential for comparing generic and brand-name drugs in these types of studies. Drug equivalency is assessed utilizing procedures such as confidence interval estimations and bioequivalence testing³⁶.

Pharmacoepidemiology:

Statistical methods are used in pharmacoepidemiologic studies to evaluate safety profiles, real-world efficacy, and drug consumption trends. Drug outcomes in a wide range of patient populations can be studied using observational studies and meta-analyses³⁷.

Administrations of Nanocrystals in Different Routes:

Oral Administration:

Nanocrystals can improve the oral bioavailability of poorly soluble medicines by enhancing dissolution velocity and saturation solubility. This method is very useful for increasing the absorption of medicines with low solubility in the gastrointestinal tract. Nanocrystals can be made into tablets, capsules, or solutions for oral administration, making it easier for patients to take their medication³⁸.

Parenteral Administration:

Because of their small particle size and improved solubility, nanocrystals can be delivered parenterally, including by intravenous injection. Nanocrystals can circumvent the gastrointestinal tract and reach the circulation directly, resulting in fast medication delivery and excellent bioavailability. Nanocrystals injected intravenously have demonstrated comparable pharmacokinetic properties to drug solutions, demonstrating their potential for effective systemic administration³⁸.

Ocular Administration:

Nanocrystals provide a possible approach for ocular administration of poorly soluble medicines due to their restricted solubility in lachrymal fluids. Nanocrystals can increase the drug's saturation solubility, resulting in higher drug concentrations at the site of action. Their sticky characteristics help prevent medication loss and lengthen residence time in the eye, hence improving the efficiency of ocular drug administration^37,38.

Pulmonary Administration:

Aerosols containing nanocrystals can be used to deliver poorly soluble medicines to the lungs. Traditional microparticle aerosols may have difficulties such as mouth deposition and low medication solubility, whereas nanocrystal-based aerosols provide better bioavailability. Nanocrystals can be nebulized and inhaled, offering a direct pathway for medication absorption in the lungs and potentially improving treatment outcomes^37,38.

Topical administration:

Topical nanocrystals improve skin penetration and drug administration for dermatological conditions, although they have stability and aggregation issues on the skin. Their compact size and increased surface area promote deeper skin absorption, with surface changes critical for penetration and long-term release. Nanocrystals are useful in treating fungal infections and inflammatory disorders, with regulated release improving medicine retention and therapeutic efficacy. Mastery of skin penetration processes and formulation refinement are essential for realizing nanocrystals' promise in dermatological therapies^37,38.

CONCLUSION:

The potential of nanocrystalline formulations to improve topical and transdermal medication delivery has been shown. They are an incredibly adaptable delivery strategy since they can be used to boost permeability and solubility even for poorly water-soluble medications. Even though more research is required to determine therapeutic efficacy, scale-up production, and biocompatibility, the field has grown tremendously in the last ten years. Commercial products and available clinical data demonstrate the translational advancement of nanocrystals. As carriers for topical drug administration, nanocrystals have the potential to significantly impact medicine delivery with further research and development.

ACKNOWLEDGMENT:

The authors would like to thank the Department of Science and Technology - Fund for Improvement of Science and Technology Infrastructure (DST-FIST) and Promotion of University Research and Scientific Excellence (DST-PURSE) for the facilities provided for conducting the research.

CONFLICT OF INTEREST:

The authors have no conflicts of interest.

REFERENCE:

1. Gaikwad NA, Pujari AS, Mane IV, et al. Formulation and Characterization of Atorvastatin Nanocystal Tablet. Asian Journal of Pharmacy and Technology. 2019; 9(2): 99-106. doi: 10.5958/2231-5713.2019.00017.5

2. Neha Xalxo, Anup Naha, Abhishek Dhoot, et al. Nanocrystals: A Newer Technological Advancement in Drug Delivery. Research Journal of Pharmacy and Technology. 2018; 11(4): 1685-1690. doi: 10.5958/0974-360X.2018.00314.1

3. Puppala Raman Kumar, Vijaya Lakshmi A. An Overview on Nanobased Drug Delivery System. Research Journal of Pharmacy and Technology. 2020; 13(10): 4996-5003. doi: 10.5958/0974-360X.2020.00875.6

4. Balram, Navneet Kaur, Kamal, et al. Nanotechnology in Herbal Drug Delivery Systems: Enhancing Therapeutic Efficacy and patient compliance. Research Journal of Pharmacy and Technology. 2024; 17(2): 934-8. doi: 10.52711/0974-360X.2024.00145

5. Mst. Mahfuza Rahman, Md. Kouser, Uthpall Kumar Roy, et al. The Significance and Implications of Nanotechnology in COVID-19. Research Journal of Pharmacy and Technology. 2023; 16(5): 2409-6. doi: 10.52711/0974-360X.2023.00411

6. Lidia Kamal Al-Halaseh, Rawan Al-Suhaimat, Duaa Al-Suhaimat, et al. Revolutionized Drug Delivery by using Pulmonary Nanotechnology: A Review. Research Journal of Pharmacy and Technology. 2023; 16(9): 4462-8. doi: 10.52711/0974-360X.2023.00728

7. Mohammad FA, Rapolu K, Valugonda SK, et al. Optimization of Cuprous Oxide Nanocrystals Deposition on Multiwalled Carbon Nanotubes. Asian Journal of Research in Chemistry. 2012; 5(1): 116-22.

8. Narwade S, Bagad D. Nanocrystals-Universal approach for poorly hydrophilic drug. Research Journal of Pharmaceutical Dosage Forms and Technology. 2013; 5(5): 245-51.

9. Sheetal S. Buddhadev, Kevinkumar C. Garala. Self-Nano Emulsifying Drug Delivery System: A Potential Solution to the Challenges of Oral Delivery of Poorly Water-Soluble Drugs. Research Journal of Pharmacy and Technology. 2023; 16(10): 4943-51. doi: 10.52711/0974-360X.2023.00801

10. Selvakumar Kalimuthu, AV Yadav. Nanobased Drug Delivery System: A Review. Research Journal of Pharmacy and Technology. 2009; 2(1): Jan.-Mar. 21-27.

11. Shachi R. Patel, Dhiren P. Shah. A Review on Nanocrystals Drug Delivery System. Research Journal of Pharmacy and Technology. 2015; 8(5): 647-654. doi: 10.5958/0974-360X.2015.00103.1

12. Abdul Hasan Sathali. A, Jeya Chandra Prakash. S.K. Formulation and Evaluation of Amisulpride Nanocrystal Tablets. Research Journal of Pharmacy and Technology. 8(9): Sept., 2015; Page 1294-1306. doi: 10.5958/0974-360X.2015.00235.8

13. Navdeep Singh, Shivi Sondhi, Sanyam Sharma, et al. Treatment of Skin Cancer by Topical Drug Delivery of Nanoparticles: A Review. Research Journal of Pharmacy and Technology 2021; 14(10):5589-8. doi: 10.52711/0974-360X.2021.00973

14. Yadav AR, Mohite SK. Applications of nanotechnology in cosmeceuticals. Research Journal of Topical and Cosmetic Sciences. 2020;11(2):83-8. doi: 10.5958/2321-5844.2020.00015.1

15. Runa Chakravorty. Nanosuspension as an emerging Nanotechnology and Techniques for its Development. Research Journal of Pharmacy and Technology. 2022; 15(1):489-3. doi: 10.52711/0974-360X.2022.00079

16. Rahul Krishnan P R, Sivakumar R. Nanotechnology: Modern Formulation and Evaluation Techniques - An Overview. Research Journal of Pharmacy and Technology. 2019; 12(8): 4039-4044. doi: 10.5958/0974-360X.2019.00696.6

17. Bandivadekar Mithun Mohanrao, Pancholi Shyam Sundar, Shelke Nagsen. Oral bioavailability enhancement of a poor water soluble drug by co-surfactant free self-emulsifying drug delivery system (SEDDS). Research Journal of Pharmacy and Technology. 4(10): Oct. 2011; 1557-1562.

18. Sanket Rathod, Ketaki Shinde, Namdeo Shinde, et al. Cosmeceuticals and Nanotechnology in Beauty Care Products. Research Journal of Topical and Cosmetic Sciences. 2021; 12(2):93-1. doi: 10.52711/2321-5844.2021.00013

19. Saurabh Tiwari, Shweta Singh, Pushpendra Kumar Tripathi. A Review- Nanogel Drug Delivery System. Asian Journal of Research in Pharmaceutical Science. 2015;5(4):253-5. doi: 10.5958/2231-5659.2015.00037.5

20. Syed Zia ul Quasim, Mohd Irfan Ali, Syed Irfan, et al. Advances in Drug Delivery System: Carbon Nanotubes. Research Journal of Pharmacy and Technology. 2013 Feb; 6(2): 125-129.

21. Agarwal V,Kaushik N, Sharma P. Nanocrystal Approaches for Poorly Soluble Drugs and their Role in Development of Marketed Formulation. Drug Delivery Letters. 2021 Dec 1;11(4):275-94. doi: 11. 10.2174/2210303111666210616115543.

22. Mishra R, Kulkarni S, Aher A, et al. One pot development of lipid-based quercetin spherical agglomerates for bioavailability enhancement: in vitro and in vivo assessments. International Journal of Applied Pharmaceutics. 2023;15(3):168-77. doi: 10.22159/ijap.2023v15i3.47266

23. Permana AD, Utami RN, Layadi P, et al. Thermosensitive and mucoadhesive in situ ocular gel for effective local delivery and antifungal activity of itraconazole nanocrystal in the treatment of fungal keratitis. International Journal of Pharmaceutics. 2021 Jun 1;602: 120623. doi: 10.1016/j.ijpharm.2021.120623.

24. Malamatari M, Taylor KMG, Malamataris S, et al. Pharmaceutical nanocrystals: production by wet milling and applications. Drug Discovery Today. 2018 Mar 1;23(3):534-47. doi: 10.1016/j.drudis.2018.01.016.

25. Parmar PK, Wadhawan J, Bansal AK. Pharmaceutical nanocrystals: A promising approach for improved topical drug delivery. Drug Discovery Today. 2021 Oct 1;26(10):2329-49. doi:10.1016/j.drudis.2021.07.010

26. Peltonen L, Hirvonen J. Drug nanocrystals - Versatile option for formulation of poorly soluble materials. International Journal of Pharmaceutics. 2018 Feb 15;537(1-2):73-83. doi: 10.1016/j.ijpharm.2017 .12.005.

27. Chang D, Ma Y, Cao G, et al. Improved oral bioavailability for lutein by nanocrystal technology: formulation development, in vitro and in vivo evaluation. Artificial Cells, Nanomedicine and Biotechnology. 2018 Jul 4; 46(5):1018-24. doi: 10.1080/21691401.2017.1358732.

28. Shinde A, Jadhav N, More H, et al. Design and characterisation of lopinavir nanocrystals for solubility and dissolution enhancement. Pharmaceutical Sciences Asia. 2019 Jul 1; 46:193-205. doi: 10.29090/psa.2019.03.018.0020.

29. Pattnaik S, Swain K, Rao JV, et al. Aceclofenac nano crystals for improved dissolution: Influence of polymeric stabilizers. RSC Advances (5). 2015;5(112):91960-5. doi: 10.10 39/C5RA20411A.

30. Kurakula M, El-Helw AM, Sobahi TR, et al. Chitosan based atorvastatin nano crystals: Effect of cationic charge on particle size, formulation stability, and in-vivo efficacy. International Journal of Nanomedicine. 2015 Jan 6:321-34. doi: 10.2147/IJN.S77731.

31. Gigliobianco MR, Casadidio C, Censi R, et al. Nanocrystals of poorly soluble drugs: Drug bioavailability and physicochemical stability. Pharmaceutics. 2018 Aug 21;10(3):134. doi: 10.3390/pharmaceutics10030134.

32. Sharma OP, Patel V, Mehta T. Nanocrystal for ocular drug delivery: hope or hype. Drug Delivery and Translational Research. 2016 Aug; 6: 399-413. doi: 10.1007/s13346-016-0292-0.

33. Chang D, Ma Y, Cao G, et al. Improved oral bioavailability for lutein by nanocrystal technology: formulation development, in vitro and in vivo evaluation. Artificial Cells, Nanomedicine and Biotechnology. 2018 Jul 4;46(5):1018-24. doi: 10.1080/21691401.2017.1358732.

34. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. Journal of pharmacy and pharmacology. 2010 Nov;62(11):1607-21. doi: 10.1111/j.2042-7158.2010.01030.x.

35. Chogale MM, Ghodake VN, Patravale VB. Performance parameters and characterizations of nanocrystals: A brief review. Pharmaceutics. 2016 Aug 30;8(3):26. doi: 10.3390/pharmaceutics8030026

36. Price DJ, Nair A, Kuentz M, et al. Calculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulations. European Journal of Pharmaceutical Sciences. 2019 Apr 30;132:142-56. doi: 10.1016/j.ejps.2019.03.006

37. Dhaval M, Makwana J, Sakariya E, et al. Drug nanocrystals: a comprehensive review with current regulatory guidelines. Current drug delivery. 2020 Jul 1;17(6):470-82. doi: 10.2174/1567201817666200512104833.

38. Smart JD. The basics and underlying mechanisms of mucoadhesion. Advanced drug delivery reviews. 2005 Nov 3;57(11):1556-68. doi: 10.1016/j.addr.2005.07.001.

39. Mohammad IS, Hu H, Yin L, et al. Drug nanocrystals: Fabrication methods and promising therapeutic applications. International journal of pharmaceutics. 2019 May 1;562:187-202. doi: 10.1016/j.ijpharm.2019.02.045

40. Chan HK, Kwok PC. Production methods for nanodrug particles using the bottom-up approach. Advanced drug delivery reviews. 2011 May 30;63(6):406-16. doi: 10.1016/j.addr.2011.03.011.

41. Butler JM, Dressman JB. The developability classification system: application of biopharmaceutics concepts to formulation development. Journal of pharmaceutical sciences. 2010 Dec 1;99(12):4940-54. doi: 10.1002/jps.22217

42. Gopu B, Pandian R, Sevvel A, et al. Routes of Nano-drug Administration and Nano-based Drug Delivery System and Toxicity. InBiomedical Applications and Toxicity of Nanomaterials 2023 May 9 (pp. 671-702). doi:10.1007/978-981-19-7834-0_25

43. Pınar SG, Oktay AN, Karaküçük AE, et al. Formulation strategies of nanosuspensions for various administration routes. Pharmaceutics. 2023 May 17;15(5):1520. doi: 10.3390/pharmaceutics15051520

44. Gigliobianco MR, Casadidio C, Censi R, et al. Nanocrystals of poorly soluble drugs: drug bioavailability and physicochemical stability. Pharmaceutics. 2018 Aug 21;10(3):134. doi: 10.3390/pharmaceutics10030134

45. McGuckin MB, Wang J, Ghanma R, et al. Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. Journal of Controlled Release. 2022 May 1;345:334-53. doi:10.1016/j.jconrel.2022.03.012

46. Ghasemiyeh P, Mohammadi-Samani S. Potential of nanoparticles as permeation enhancers and targeted delivery options for skin: Advantages and disadvantages. Drug design, development and therapy. 2020 Aug 12:3271-89.

47. Raina N, Rani R, Thakur VK, et al. New insights in topical drug delivery for skin disorders: from a nanotechnological perspective. ACS omega. 2023 May 19;8(22):19145-67. doi: 10.1021/acsomega.2c08016

48. Yu YQ, Yang X, Wu XF, et al. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: novel strategies for effective transdermal applications. Frontiers in bioengineering and biotechnology. 2021 Mar 29;9:646554. Doi: 10.3389/fbioe.2021.646554

Received on 03.10.2024 Revised on 22.02.2025

Accepted on 28.04.2025 Published on 13.01.2026

Available online from January 17, 2026

Research J. Pharmacy and Technology. 2026;19(1):446-451.

DOI: 10.52711/0974-360X.2026.00065

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Trade name with API	Uses	Applied technology	Manufacturer	Formulation
Invega Sustenna® (Paliperidone palmitate)	Treat major depressive disorder	Wet Bead Milling, High pressure homogenization	Johnson & Johnson	Tablet
Cesamet® (Nabilone)	Used as anti-emetic	Precipitation	Lilly	Capsule
Naprelan® (naproxen sodium)	Anti-inflammatory	Wet Bead Milling	Wyeth	Tablet
Theodur® (Theophylline)	Treat Bronchial dilation	Wet Bead Milling	Mitsubishi Tanabe Pharma	Tablet, Capsule
Herbesser® (Diltiazem HCl)	Used as Anti-angina	Wet Bead Milling	Mitsubishi Tanabe Pharma	Tablet
Zanaflex™ (Tizanidine HCl)	Used as Muscle relaxant	Wet Bead Milling	Acorda	Capsule
FocalinXR® (Dexmethyl- phenidate HCl)	Used as Anti-psychotic	Wet Bead Milling	Novartis	Capsule
Azopt® (Brinzolamide)	Treat Glaucoma	Wet Bead Milling	Alcon	Suspension
Ritalin LA® (Methyl-phenidate HCl)	Used as Anti-psychotic	Wet Bead Milling	Novartis	Capsule
Rapamune (Rapamycin)	Immunosuppressive drug	Wet Bead Milling	Wyeth	Tablet
Emend (Aprepitant)	Used as anti-emetic	Wet Bead Milling	Merck	Capsule
Tricor (Fenofibrate)	Hyperlipidemia	Wet Bead Milling	Abbott	Tablet