3D Printing of Dapagliflozin Containing Self-Nanoemulsifying Tablets: Formulation Design and In Vitro Characterization

The 3D printing techniques have been explored extensively in recent years for pharmaceutical manufacturing and drug delivery applications. The current investigation aims to explore 3D printing for the design and development of a nanomedicine-based oral solid dosage form of a poorly water-soluble drug. A self-nanoemulsifying tablet formulation of dapagliflozin propanediol monohydrate was developed utilizing the semisolid pressure-assisted microsyringe (PAM) extrusion-based 3D printing technique. The developed formulation system consists of two major components (liquid and solid phase), which include oils (caproyl 90, octanoic acid) and co-surfactant (PEG 400) as liquid phase while surfactant (poloxamer 188) and solid matrix (PEG 6000) as solid-phase excipients that ultimately self-nanoemulsify as a drug encapsulated nanoemulsion system on contact with aqueous phase/gastrointestinal fluid. The droplet size distribution of the generated nanoemulsion from a self-nanoemulsifying 3D printed tablet was observed to be 104.7 ± 3.36 nm with polydispersity index 0.063 ± 0.024. The FT-IR analysis of the printed tablet revealed that no drug-excipients interactions were observed. The DSC and X-RD analysis of the printed tablet revealed that the loaded drug is molecularly dispersed in the crystal lattice of the tablet solid matrix and remains solubilized in the liquid phase of the printed tablet. SEM image of the drug-loaded self-nanoemulsifying tablets revealed that dapagliflozin propanediol monohydrate was completely encapsulated in the solid matrix of the printed tablet, which was further confirmed by SEM-EDS analysis. The in vitro dissolution profile of dapagliflozin-loaded self-nanoemulsifying tablet revealed an immediate-release drug profile for all three sizes (8 mm, 10 mm, and 12 mm) tablets, exhibiting >75.0% drug release within 20 min. Thus, this study has emphasized the capability of the PAM-based 3D printing technique to print a self-nanoemulsifying tablet dosage form with an immediate-release drug profile for poorly water-soluble drug

Assessment of Pharmacist’s Knowledge and Perception toward 3D Printing Technology as a Dispensing Method for Personalized Medicine and the Readiness for Implementation

The main user of three dimensional (3D) printing for drug dispensing will be the hospital pharmacist. Yet despite the tremendous amount of research and industrial initiatives, there is no evaluation of the pharmacist’s knowledge and opinion of this technology. The present study aimed to assess knowledge and attitude among pharmacists about 3D printing technology as an innovative dispensing method for personalized medicine and the barriers to implementation in Saudi Arabia. We found that 53% of participants were aware of 3D printing technology in general, but only 14–16% of pharmacists were aware of the specific application of 3D printing in drug dispensing. Participants showed a positive perception regarding the concept of personalized medicine and that 3D printing could provide a promising solution to formulate and dispense personalized medicine in the pharmacy. It was also found that 67% of pharmacists were encouraged to adopt this new technology for drug dispensing, reflecting their willingness to learn new innovations. However, the technology cost, regulation, and the shortage of practicing pharmacists were also reported as the top barriers for implementation. Facilitating the implementation of this technology in the pharmacy practice will require a strategic plan in which pharmacists collaborate with regulatory bodies and 3D printing engineers to overcome challenges and barriers to implement such promising technology

Preparation and Characterization of Curcumin Nanoemulgel Utilizing Ultrasonication Technique for Wound Healing: In Vitro, Ex Vivo, and In Vivo Evaluation

Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin

Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets

The use of 3D printing techniques to control drug release has flourished in the past decade, although there is no generic solution that can be applied to the full range of drugs or solid dosage forms. The present study provides a new concept, using the 3D printing technique to print a coating system in the form of shells with various designs to control/modify drug release in immediate-release tablets. A coating system of cellulose acetate in the form of an encapsulating shell was printed through extrusion-based 3D printing technology, where an immediate-release propranolol HCl tablet was placed inside to achieve a sustained drug release profile. The current work investigated the influence of shell composition by using different excipients and also by exploring the impact of shell size on the drug release from the encapsulated tablet. Three-dimensional printed shells with different ratios of rate-controlling polymer (cellulose acetate) and pore-forming agent (D-mannitol) showed the ability to control the amount and the rate of propranolol HCl release from the encapsulated tablet model. The shell-print approach also showed that space/gap available for drug dissolution between the shell wall and the enclosed tablet significantly influenced the release of propranolol HCl. The modified release profile of propranolol HCl achieved through enclosing the tablet in a 3D printed controlled-release shell followed Korsmeyer–Peppas kinetics with non-Fickian diffusion. This approach could be utilized to tailor the release profile of a Biopharmaceutics Classification System (BCS) class I drug tablet (characterized by high solubility and high permeability) to improve patient compliance and promote personalized medicine

Investigation of Factors Influencing Formation of Nanoemulsion by Spontaneous Emulsification: Impact on Droplet Size, Polydispersity Index, and Stability

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. In the present study, we investigate the influence of intricate factors including composition and preparation conditions that affect characteristic parameters and the stability of the nanoemulsion formation prepared by the spontaneous emulsification method. Octanoic acid, capryol 90, and ethyl oleate were selected to represent oil phases of different carbon–chain lengths. We explored the impact of the addition mode of the oil–Smix phase and aqueous phase, vortexing time, Km (surfactant/cosurfactant) ratio, and the replacement of water by buffers of different pH as an aqueous system. The phase behavior study showed that the Smix phase had a significant impact on the nanoemulsifying ability of the nanoemulsions composed of oil phases of varying carbon-chain lengths. The mode of mixing of the oil–Smix phase to the aqueous phase markedly influenced the mean droplet size and size distribution of the nanoemulsions composed of oil phases as capryol 90. Vortexing time also impacted the mean droplet size and the stability of the generated nanoemulsion system depending on the varying carbon-chain length of the oil phase. The replacement of the water phase by aqueous buffers of pH 1.2, 5.5, 6.8, and 7.4 has altered the mean droplet size and size distribution of the nanoemulsion system. Further, the Km ratio also had a significant influence on the formation of the nanoemulsion system. The findings of this investigation are useful in understanding how the formulation composition and process parameters of the spontaneous emulsification technique are responsible for affecting the physicochemical characteristics and stability of the nanoemulsion system composed of oil of varying carbon-chain (C8-C18) length

Nanoscale Topical Pharmacotherapy in Management of Psoriasis: Contemporary Research and Scope

Psoriasis is a typical dermal condition that has been anticipated since prehistoric times when it was mistakenly implicit in being a variant of leprosy. It is an atypical organ-specific autoimmune disorder, which is triggered by the activation of T-cells and/or B-cells. Until now, the pathophysiology of this disease is not completely explicated and still, many research investigations are ongoing. Different approaches have been investigated to treat this dreadful skin disease using various anti-psoriatic drugs of different modes of action through smart drug-delivery systems. Nevertheless, there is no ideal therapy for a complete cure of psoriasis owing to the dearth of an ideal drug-delivery system for anti-psoriatic drugs. The conventional pharmacotherapy approaches for the treatment of psoriasis demand various classes of anti-psoriatic drugs with optimum benefit/risk ratio and insignificant untoward effects. The advancement in nanoscale drug delivery had a great impact on the establishment of a nanomedicine-based therapy for better management of psoriasis in recent times. Nanodrug carriers are exploited to design and develop nanomedicine-based therapy for psoriasis. It has a promising future in the improvement of the therapeutic efficacy of conventional anti-psoriatic drugs. The present manuscript aims to discuss the pathophysiology, conventional pharmacotherapy, and contemporary research in the area of nanoscale topical drug delivery systems for better management of psoriasis including the significance of targeted pharmacotherapy in psoriasis

Preparation and Characterization of Curcumin Nanoemulgel Utilizing Ultrasonication Technique for Wound Healing: In Vitro, Ex Vivo, and In Vivo Evaluation

Hydrogels being a drug delivery system has great significance particularly for topical application in cutaneous open wound. Its specific physicochemical properties such as non-adhesiveness, moisture retention, exudate absorption, and gas permeability make them ideal as a drug delivery vehicle for wound healing application. Further, curcumin (a natural bioactive) was selected as a therapeutic agent to incorporate into the hydrogel system to design and develop nanogel pharmaceutical products for wound healing. Although, curcumin possesses remarkable anti-inflammatory, antioxidant, and anti-infective activity along with hastening the healing process by acting over the different stages of the wound healing process, but its poor biopharmaceutical (low aqueous solubility and skin penetrability) attributes hamper their therapeutic efficacy for skin applications. The current investigation aimed to develop the curcumin-loaded nanogel system and evaluated to check the improvement in the therapeutic efficacy of curcumin through a nanomedicine-based approach for wound healing activity in Wistar rats. The curcumin was enclosed inside the nanoemulsion system prepared through a high-energy ultrasonic emulsification technique at a minimum concentration of surfactant required to nanoemulsify the curcumin-loaded oil system (Labrafac PG) having droplet size 56.25 ± 0.69 nm with polydispersity index 0.05 ± 0.01 and negatively surface charge with zeta potential −20.26 ± 0.65 mV. It was observed that the impact of Smix (surfactant/co-surfactant mixture) ratio on droplet size of generated nanoemulsion is more pronounced at lower Smix concentration (25%) compared to the higher Smix concentration (30%). The optimized curcumin-loaded nanoemulsion was incorporated into a 0.5% Carbopol® 940 hydrogel system for topical application. The developed curcumin nanoemulgel exhibited thixotropic rheological behavior and a significant (p < 0.05) increase in skin penetrability characteristics compared to curcumin dispersed in conventional hydrogel system. The in vivo wound healing efficacy study and histological examination of healed tissue specimen further signify the role of the nanomedicine-based approach to improve the biopharmaceutical attributes of curcumin

Thymoquinone Loaded Topical Nanoemulgel for Wound Healing: Formulation Design and In-Vivo Evaluation

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to &lt;100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p &lt; 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p &lt; 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study

High throughput screening for biomaterials discovery

Using microarray technologies thousands of biomedical materials can be screened in a rapid, parallel and cost effective fashion to identify the optimum candidate that fulfils a specific biomedical application. High throughput surface characterization (HTSC) of printed microarrays has played a key role in the discovery and development of biomedical materials. This review focuses on the production and HTSC of microarrays, their application in specific biomedical fields and a future perspective on the development of this technology

Development of a Curcumin-Loaded Lecithin/Chitosan Nanoparticle Utilizing a Box-Behnken Design of Experiment: Formulation Design and Influence of Process Parameters

Curcumin (CUR) has impressive pharmacologic properties, including cardioprotective, neuroprotective, antimicrobial, and anticancer activity. However, the pharmaceutical application of CUR is limited due to its poor aqueous solubility and low bioavailability. The development of novel formulations has attracted considerable attention to the idea of applying nanobiotechnology to improve the therapeutic efficacy of these challenging compounds. In this study, CUR-loaded lecithin–chitosan nanoparticles (CUR/LCSNPs) were developed and optimized by the concentration of chitosan, lecithin, and stirring speed by a 3-factorial Box-Behnken statistical design, resulting in an optimal concentration of chitosan (A) and lecithin (B) with a 1200 rpm stirring speed (C), with applied constraints of minimal average particle size (Y1), optimal zeta potential (Y2), and maximum entrapment efficiency (%EE) (Y3). The mean particle size of the checkpoint formulation ranged from 136.44 ± 1.74 nm to 267.94 ± 3.72, with a zeta potential of 18.5 ± 1.39 mV to 36.8 ± 3.24 mV and %EE of 69.84 ± 1.51% to 78.50 ± 2.11%. The mean particle size, zeta potential, %EE, and % cumulative drug release from the optimized formulation were 138.43 ± 2.09 nm, +18.98 ± 0.72 mV, 77.39 ± 1.70%, and 86.18 ± 1.5%, respectively. In vitro drug release followed the Korsmeyer–Peppas model with Fickian diffusion (n < 0.45). The optimized technique has proven successful, resulting in a nanoformulation that can be used for the high loading and controlled release of lipophilic drugs