Harmonising IV Oxycodone with Paediatric Perioperative Medications: A Compatibility Study Through Y-Type Connectors.

Purpose: Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids. Methods: Mixtures of oxycodone (1mg.mL-1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150. Results: IV oxycodone (1 mg.mL-1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested. Conclusion: According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL-1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.

Enhanced Skin Permeation of 5-Fluorouracil through Drug-in-Adhesive Topical Patches.

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles.

Printing a cure: A tailored solution for localized drug delivery in liver cancer treatment.

Adjuvant chemotherapy is highly recommended for liver cancer to enhance survival rates due to its tendency to recur frequently. Localized drug-eluting implants have gained traction as an alternative to overcome the limitations of systemic chemotherapy. This work describes the development of biodegradable 3D printed (3DP) bilayer films loaded with 5-fluorouracil (5FU) and cisplatin (Cis) with different infill percentages where the 5FU layers were 40%, 30%, and 30% and Cis layers were 10%, 15%, and 10% for films A, B, and C, respectively. The relevant characterization tests were performed, and the drug content of films was 0.68, 0.50, and 0.50 mg of 5FU and 0.39, 0.80, and 0.34 mg of Cis for films A, B, and C, respectively. Cis release was affected by the alterations to the film design, where films A, B, and C showed complete release at 12, 14, and 23 days, respectively. However, 5FU was released over 24 h for all films. The films were stable for up to two weeks after storage at 25 °C/65% relative humidity and four weeks at 4 °C where drug content, tensile strength, FTIR, and thermal analysis results demonstrated negligible alterations. The cytotoxicity of the films was assessed by MTS assays using HepG2 cell lines demonstrating up to 81% reduction in cell viability compared to blank films. Moreover, apoptosis was confirmed by Western Blots and the determination of mitochondrial cell potential, highlighting the potential of these films as a promising approach in adjuvant chemotherapy.

Combining the potential of 3D printed buccal films and nanostructured lipid carriers for personalised cannabidiol delivery.

Cannabidiol (CBD) has been recognized for its numerous therapeutic benefits, such as neuroprotection, anti-inflammatory effects, and cardioprotection. However, CBD has some limitations, including unpredictable pharmacokinetics and low oral bioavailability. To overcome the challenges associated with CBD delivery, we employed Design of Experiments (DoE), lipid carriers, and 3D printing techniques to optimize and develop buccal film loaded with CBD-NLCs. Three-factor Box-Behnken Design was carried out to optimise the NLCs and analyse the effect of independent factors on dependent factors. The emulsification-ultrasonication technique was used to prepare the NLCs. A pressure-assisted micro-syringe printing technique was used to produce the films. The produced films were studied for physicochemical, and mechanical properties, release profiles, and predicted in vivo performance. The observed particle size of the NLCs ranged from 12.17 to 84.91 nm whereas the PDI varied from 0.099 to 0.298. Lipid and sonication time positively affected the particle size whereas the surfactant concentration was inversely related. CBD was incorporated into the optimal formulation and the observed particle size, PDI, and zeta potential for the CBD-NLCs were 94.2 ± 0.47 nm, 0.11 ± 0.01 and - 11.8 ± 0.52 mV. Hydroxyethyl cellulose (HEC)-based gel containing the CBD-NLCs was prepared and used as a feed for 3D printing. The CBD-NLCs film demonstrated a slow and sustained in vitro release profile (84. 11 ± 7.02% in 6 h). The predicted AUC0-10 h, Cmax, and Tmax were 201.5 µg·h/L, 0.74 µg/L, and 1.28 h for a film with 0.4 mg of CBD, respectively. The finding demonstrates that a buccal film of CBD-NLCs can be fabricated using 3D printing.

Innovative Topical Patches for Non-Melanoma Skin Cancer: Current Challenges and Key Formulation Considerations.

Non-melanoma skin cancer (NMSC) is the most prevalent malignancy worldwide, with approximately 6.3 million new cases worldwide in 2019. One of the key management strategies for NMSC is a topical treatment usually utilised for localised and early-stage disease owing to its non-invasive nature. However, the efficacy of topical agents is often hindered by poor drug penetration and patient adherence. Therefore, various research groups have employed advanced drug delivery systems, including topical patches to overcome the problem of conventional topical treatments. This review begins with an overview of NMSC as well as the current landscape of topical treatments for NMSC, specifically focusing on the emerging technology of topical patches. A detailed discussion of their potential to overcome the limitations of existing therapies will then follow. Most importantly, to the best of our knowledge, this work unprecedentedly combines and discusses all the current advancements in innovative topical patches for the treatment of NMSC. In addition to this, the authors present our insights into the key considerations and emerging trends in the construction of these advanced topical patches. This review is meant for researchers and clinicians to consider utilising advanced topical patch systems in research and clinical trials toward localised interventions of NMSC.

Nanotechnology and narasin: a powerful combination against acne.

Acne vulgaris is widely regarded as the most prevalent skin disorder characterized by painful, inflammatory skin lesions that are primarily attributed to the pathogenic actions of Cutibacterium acnes (C. acnes). To improve the clinical management of this disease, there is a pressing clinical demand to develop innovative antibacterial therapies that utilize novel mechanisms. The current research aimed to discover the antibacterial efficacy of narasin (NAR), a polyether ionophore, against drug-resistant acne bacteria. In addition, the study aimed to formulate self-nanomicellizing solid dispersions (SNMSD), utilizing Soluplus® (SOL), as a drug delivery system to incorporate NAR and selectively target the lipophilic C. acnes abundant environments within the skin. Furthermore, the study aimed to investigate the ex vivo deposition and permeation of NAR into the various layers of the skin using full-thickness porcine ear skin as a model skin. By encapsulating NAR within spherical polymeric micelles (dn < 80 nm) aqueous solubility was significantly increased by approximately 100-fold (from <40 µg mL-1 to 4600 µg mL-1). Following optimization, the micelle solution was integrated into a gel formulation (containing 0.2% w/v NAR) and evaluated for stability over 4 weeks at room temperature (drug content >98%). Results from drug deposition and permeation experiments demonstrated that the deposition of NAR from the NAR-micelle solution and its gel formulation into the lipophilic stratum corneum (19 835.60 ± 6237.89 ng cm-2 and 40 601.14 ± 3736.09 ng cm-2) and epidermis (19 347 ± 1912.98 ng cm-2 and 18 763.54 ± 580.77 ng cm-2) was superior to that of NAR in solution, which failed to penetrate any skin layers. In conclusion, the outcomes of this study provide evidence that NAR exhibits promising activity against antimicrobial resistant strains of C. acnes (MIC range ≤0.008-0.062) and that micelle nanocarriers can improve the aqueous solubility of poorly water-soluble drugs. Furthermore, our results highlight the ability of nanomicelles to enable selective and targeted drug delivery to the lipophilic skin layers.

Application of Exogenous GnRH in Food Animal Production.

Over several decades, exogenous GnRH and agonists have been employed for controlling reproductive cascades in animals, and treating some reproductive morbidities. The administration of GnRH is used in animals to counter ovarian dysfunction, induce ovulation, and to increase conception and pregnancy rates. GnRH and its agonists are used in the treatment of cystic ovarian degeneration and repeat breeder syndrome. The development of protocols for GnRH administration by intramuscular injection, intramuscular or subcutaneous implants, and intravaginal deposition has empowered their clinical use worldwide. Currently, exogenous GnRH products are a central part of several pre- and post-breeding programs for the enhancement of fertility, including the control of estrous cycles and timing of ovulation, development of fixed-time artificial insemination protocols, improved embryo survival, and the treatment of reproductive morbidity. The aim of the present review is to summarize the application of exogenous GnRH agonists in food animal production.

The Management of Parkinson's Disease: An Overview of the Current Advancements in Drug Delivery Systems.

Parkinson's disease (PD) has significantly affected a large proportion of the elderly population worldwide. According to the World Health Organization, approximately 8.5 million people worldwide are living with PD. In the United States, an estimated one million people are living with PD, with approximately 60,000 new cases diagnosed every year. Conventional therapies available for Parkinson's disease are associated with limitations such as the wearing-off effect, on-off period, episodes of motor freezing, and dyskinesia. In this review, a comprehensive overview of the latest advances in DDSs used to reduce the limitations of current therapies will be presented, and both their promising features and drawbacks will be discussed. We are also particularly interested in the technical properties, mechanism, and release patterns of incorporated drugs, as well as nanoscale delivery strategies to overcome the blood-brain barrier.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Background: Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Methods: Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. Results: In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. Conclusion: In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

Physicochemical properties of otic products for Canine Otitis Externa: comparative analysis of marketed products.

BACKGROUND: Otitis externa is a commonly diagnosed dermatological disorder in canines. The pathogens primarily involved in canine otitis externa (COE) include Staphylococcus pseudintermedius, Pseudomonas aeruginosa, Proteus mirabilis, and Malassezia pachydermatis. As COE tends to be superficial, medications delivered topically are often effective and practical in managing the condition. As such, there is a wide variety of approved topical products currently available in the market. The efficacy of topical dosage forms can be dependent on various factors such as the pharmacology of active constituents and the physicochemical properties of the formulation, including pH, viscosity, spreadability, and bio-adhesion. Currently, there is a lack of published literature available on the optimal properties of topical COE products. In this study, we compared the physicochemical properties of nine commercially available otic veterinarian products in Australia used clinically to manage COE. RESULTS: Based on our comparative analysis, the pH (6.26 ± 0.04) of an aqueous-based product was similar to a healthy dog's external auditory canal. Products containing polymers exhibited higher viscosity and bio-adhesion. Spreadability was inversely related to viscosity and Osurnia ® a product with high viscosity demonstrated the lowest spreadability. Aqueous-based otic products showed better syringebility whereas oil-based systems required higher force to expel the products. Variability in droplet size was noted. Derm Otic, Baytril Otic, and Aurizon Ear Drops had the lower standard deviation which indicates they would give a more consistent dose. CONCLUSIONS: Findings from this work provide considerations for industry researchers or formulation scientists working in the area of otic dosage formulations.

Advanced Strategies of Drug Delivery via Oral, Topical, and Parenteral Administration Routes: Where Do Equine Medications Stand?

While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery specifically for horses. Through a careful evaluation of equine anatomy and physiology, novel drug delivery systems (NDDSs) can be developed to adequately address many of the medical ailments of the horse. In addition to this, there are key considerations when delivering oral, topical, and parenteral drugs to horses, deriving from age and species variation. More importantly, NDDSs can enhance the duration of action of active drugs in animals, significantly improving owner compliance; and ultimately, enhancing the convenience of product administration. To address the knowledge gap in equine pharmaceutical formulations, this paper begins with a summary of the anatomy and physiology of the equine gastrointestinal, integumentary, and circulatory systems. A detailed discussion of potential dosage-form related issues affecting horses, and how they can be overcome by employing NDDSs is presented.

pH and its applications in targeted drug delivery.

Physiologic pH is vital for the normal functioning of tissues and varies in different parts of the body. The varying pH of the body has been exploited to design pH-sensitive smart oral, transdermal and vaginal drug delivery systems (DDS). The DDS demonstrated promising results in hard-to-treat diseases such as cancer and Helicobacter pylori infection. In some cases, a change in pH of tissues or body fluids has also been employed as a useful diagnostic biomarker. This paper aims to comprehensively review the development and applications of pH-sensitive DDS as well as recent advances in the field.

Influence of Acidic pH on Wound Healing In Vivo: A Novel Perspective for Wound Treatment.

There has been little understanding of acidification functionality in wound healing, highlighting the need to study the efficacy of wound acidification on wound closure and cellular activity in non-infected wounds. This study is focused on establishing the healing potential of wound acidification in non-infected wounds. Acidic buffers, constituting either phosphoric or citric acid, were employed to modify the physiological pH of non-infected full-thickness excisional murine wounds. Acidification of the wound by acidic buffers was found to be an effective strategy to improve wound healing. A significant improvement in wound healing parameters was observed as early as 2 days post-treatment with acidic buffers compared to controls, with faster rate of epithelialization, wound closure and higher levels of collagen at day 7. pH is shown to play a role in mediating the rate of wound healing, with acidic buffers formulated at pH 4 observed to stimulate faster recovery of wounded tissues than pH 6 buffers. Our study shows the importance of maintaining an acidic wound microenvironment at pH 4, which could be a potential therapeutic strategy for wound management.

Enhancement of the NIR Emission of Cr3+-Yb3+ Co-doped La3GaGe5O16 Phosphors by Doping Nd3+ Ions via Efficient Energy Transfer for NIR Spectroscopy Regulation.

The efficient energy transfer in La3GaGe5O16:Cr3+, Yb3+/Nd3+ and La3GaGe5O16:Cr3+, Yb3+, Nd3+ was investigated in detail. In this phosphor, Cr3+ acts as the energy absorber (250-700 nm) to sensitize Yb3+/Nd3+ in La3GaGe5O16. Under excitation at 418 nm, La3GaGe5O16:Cr3+, Yb3+ phosphors exhibited a broad emission band in the near-infrared (NIR) region located at 976 nm (La3GaGe5O16:Cr3+, Nd3+ at 1056 nm), which was attributed to the 2F5/2-2F7/2 transition of the Yb3+ ions (2F3/2 → 4I11/2 transition of Nd3+). Moreover, a Nd3+ ion was introduced into La3GaGe5O16:Cr3+, Yb3+. The analysis of excitation spectra and decay time proves that Nd3+ acts as a bridging ion in the system. This can be used as a new strategy to enhance the energy transfer in Cr3+, Yb3+ co-doped phosphors, and these phosphors have potential applications in NIR spectroscopy regulation.

In Vitro Wound Healing Properties of Novel Acidic Treatment Regimen in Enhancing Metabolic Activity and Migration of Skin Cells.

Strategies that alter the pH of wounds to improve healing outcomes are an emerging area of interest. Currently, there is limited understanding of the effect of hydrogen (H+) on the functionality of skin cells during proliferation and migration, highlighting the need for research to determine the effect of pH during wound healing. This study aimed to determine the effect of acidification on the metabolic activity and migration of human immortalized keratinocytes (HaCaT) and human foreskin fibroblasts (HFF). In vitro models were used with phosphoric and citric acid buffers at a pH range between 3 and 7. Our results showed that cells were more viable in buffers with low rather than high ionic strength. A time-dependent effect of the acidification treatment was also observed with cell metabolic activity varying with treatment duration and frequency. Our results showed that a 24 h treatment and subsequent resting phase significantly improved cell proliferation and migration. This in vitro study is the first to establish a correlation between the role of acidic pH, molarity and treatment regimen in cellular activity. Our data demonstrated a positive effect of acidic pH on cell metabolic activity and migration rate, suggesting a clinical potential in indications such as wound healing.

Effect of Dexamethasone and Route of Administration on Sow Farrowing Behaviours, Piglet Delivery and Litter Performance.

The inflammatory pain and stress some crated sows experience during farrowing has attendant risks of piglet-directed aggression, reduced teat exposure and hindered post-partum recovery. To counter this, the steroidal anti-inflammatory compound, dexamethasone, can be administered. To measure the potential for mucosal absorption as an alternative to injection, the permeability of porcine vaginal mucosa to dexamethasone was demonstrated using Franz cell diffusion. These studies found dexamethasone treatment diffused through vaginal mucosa at a constant rate, with 52.37 ± 5.54% permeation in 6 h. To examine in vivo effects on farrowing outcomes, dexamethasone was administered to gilts and parity one sows on the day of expected farrowing. We hypothesized that it would provide relief from farrowing discomfort and reduce behaviours threatening piglet survival. Sows were randomly assigned to receive dexamethasone as an intramuscular injection (n = 23); dexamethasone applied topically into the vagina (n = 20), or to receive no dexamethasone (n = 23). Sows (n = 66) and piglets (n = 593) were monitored for performance indicators during farrowing and early lactation. A subset of sows (n = 24) was also video monitored continuously over 24 h for behaviours associated with pain, postural changes and piglet interactions. No differences were observed between treatment for farrowing performance, piglet survival or behavioural changes for sows experiencing their first or second farrowing (p > 0.05), rejecting the hypothesis that corticosteroid administration will improve sow farrowing performance. This investigation did, however, show that dexamethasone can permeate through porcine vaginal mucosa and so can be administered as a non-injectable treatment.

Mucoadhesive Buccal Film of Estradiol for Hormonal Replacement Therapy: Development and In-Vivo Performance Prediction.

The age-related loss of circulating estrogen that occurs during the menopausal transition manifests itself through a variety of symptoms including vasomotor (hot flushes and night sweats), genito-urinary syndrome (vaginal dryness and urinary symptoms), sexual dysfunction, mood, and sleep disturbance that often last longer than a decade. Furthermore, reductions in estrogen level increase the risks of chronic complications such as osteoporosis, cardiovascular disease, and cognitive decline among others, thereby affecting the quality of life of women. Although oral estrogens are the most widely used therapy for menopausal symptoms, they suffer from poor bioavailability, and there are concerns over their safety, creating a significant concern to consumers. Mucoadhesive buccal films are an innovative dosage form that offers several advantages including avoidance of the first-pass metabolism, fast onset of action, and importantly, improved patient acceptance. In the current work, we developed mucoadhesive estradiol film for hormonal replacement therapy using film-forming polymers. Two approaches, namely, co-solvency and nano-emulsion were evaluated to increase solubility and hence incorporate estradiol, a poorly water-soluble drug, into a formulation made from the hydrophilic polymer/s. The films were characterised for their mechanical and physicochemical properties. In-vitro release study showed that about 80% of the drug was released within 6 min from films prepared by the nano-emulsion approach, whereas it took about 10.5 min to get similar drug release from films prepared by the co-solvency approach. The ex-vivo permeation result indicates that about 15% of the drug permeated across the porcine buccal mucosa in the first 10 h from films prepared by the nano-emulsion approach, while permeation across porcine buccal mucosa was only observed at around 24 h from films prepared by the co-solvency method. The nano-emulsion films were evaluated for in vivo performance using a convolution technique using R software. The predicted Cmax and Tmax were found to be 740.74 ng mL-1 and 7 min, respectively, which were higher than previously reported in vivo concentration from oral tablets. The results demonstrated that mucoadhesive film of estradiol based on the nano-emulsion approach could be a promising platform for the delivery of estradiol through the buccal mucosa for the treatment of menopausal symptoms.

Development of a Novel Vaginal Drug Delivery System to Control Time of Farrowing and Allow Supervision of Piglet Delivery.

The swine industry has evolved significantly in the recent decades, but this has come at considerable expense to piglet survival. Breeding sows for greater prolificacy has been accompanied by a greater proportion of piglets being born underweight, of lower vigor, and higher susceptibility to early mortality. Inducing sows to farrow during working hours has the potential to increase piglet survivability, but non-therapeutic injectable products are often discouraged on farms. We aimed to design and develop a novel vaginal drug delivery system (NVDDS) that could reliably trigger luteolysis and induce parturition. To achieve this, two vaginal tablets containing the luteolytic agent cloprostenol were formulated to be inserted together: one would release constituents immediately on insertion (immediate release; IR) and the other would release cloprostenol in a controlled manner (controlled release; CR). The two formulations (IR and CR) were evaluated for drug release, swelling and bio-adhesion in conditions simulating the sow vaginal environment. The IR tablet released the drug completely for 5 min whereas the CR tablet took 5 h to release 50% of the drug. Furthermore, the release kinetics were evaluated by fitting the dissolution profiles into different mathematical models. Both IR and CR tablets were best fitted by the Makoid-Banakar model which assumes release by summation of different mechanisms. The performance of the optimized formulations was studied in vivo with 161 Large White x Landrace sows of varying parity (0-5). The sows were assigned to five groups. Group 1 (SI) received a single vulval injection of cloprostenol at 0700 h (n = 32), group 2 (SDI) received the same dose split in two parts, at 0700h and 1300h (n = 33). Group 3 (IRT) animals were administered an IR tablet at 0700h (n = 32), while group 4 (IRCRT) received both IR and CR tablets at 0700 h (n = 33). Group 5 was untreated and served as a control (n = 32). The interval to farrowing was longer (p < 0.001) for controls than for treated sows, but there were no differences among cloprostenol treatments for timing of farrowing. The finding confirms the efficacy of the NVDDS for induction of farrowing in sows.

Effect of plasticizers on drug-in-adhesive patches containing 5-fluorouracil.

Topical patches containing 5-fluorouracil (5-FU) are a feasible alternative to overcome the shortcomings of commercial cream for the treatment of non-melanoma skin cancer (NMSC). Plasticizers are a critical component of drug-in-adhesive (DIA) patches as they can significantly affect the mechanical, adhesive and drug release characteristics of the patches. Eudragit® E (EuE) is a methacrylate-based cationic copolymer capable of producing flexible and adhesive films for topical application. In this study, the effect of plasticizers on the mechanical, adhesive and 5-FU release characteristics of EuE-based patches was comprehensively evaluated. While the elongation at break (%) and adhesion of the films were significantly increased with increasing triacetin, dibutyl sebacate (DBS) and triethyl citrate (TEC) concentrations, the tensile strength showed an inverse relationship. EuE plasticized with 40% triacetin, 30% DBS or 40% w/w TEC produced elastic and adhesive films most suitable for topical application. In vitro release studies of the 5-FU-loaded patches demonstrated an initial burst release pattern during the first 10 min followed by a slow release over 120 min. In summary, this study provides important information on effect of plasticizers for preparation of EuE-based patches with desired mechanical, adhesive and release characteristics of 5-FU towards their potential application in the treatment of NMSC.

3D Printing of Thermo-Sensitive Drugs.

Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.