A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson's disease.

Apomorphine, a dopamine agonist, is a highly effective therapeutic to prevent intermittent off episodes in advanced Parkinson's disease. However, its short systemic half-life necessitates three injections per day. Such a frequent dosing regimen imposes a significant compliance challenge, especially given the nature of the disease. Here, we report a deep eutectic-based formulation that slows the release of apomorphine after subcutaneous injection and extends its pharmacokinetics to convert the current three-injections-a-day therapy into an every-other-day therapy. The formulation comprises a homogeneous mixture of a deep eutectic solvent choline-geranate, a cosolvent n-methyl-pyrrolidone, a stabilizer polyethylene glycol, and water, which spontaneously emulsifies into a microemulsion upon injection in the subcutaneous space, thereby entrapping apomorphine and significantly slowing its release. Ex vivo studies with gels and rat skin demonstrate this self-emulsification process as the mechanism of action for sustained release. In vivo pharmacokinetics studies in rats and pigs further confirmed the extended release and improvement over the clinical comparator Apokyn. In vivo pharmacokinetics, supported by a pharmacokinetic simulation, demonstrate that the deep eutectic formulation reported here allows the maintenance of the therapeutic drug concentration in plasma in humans with a dosing regimen of approximately three injections per week compared to the current clinical practice of three injections per day.

Clinical Course after Carmustine Wafer Implantation for Newly Diagnosed Adult-type Diffuse Gliomas; A controlled propensity matched analysis of a single center cohort.

PURPOSE: It remains unclear whether combining carmustine wafer (CW) implantation with the standard treatment for adult-type diffuse gliomas is safe and has a prognostic impact. This study aimed to investigate the prognostic value and safety of CW implantation. METHODS: Adult patients with IDH-wild-type and -mutant gliomas, grades 3-4 treated with surgical resection, radiotherapy, and temozolomide chemotherapy between 2013 and 2023 were surveyed. CWs were implanted except in cases of intraoperative wide ventricle opening or marked preoperative brain swelling. For survival analyses, a case-matched dataset based on propensity score matching (PSM), including multiple factors (patient background, diagnosis, and extent of resection) was generated. Progression-free survival (PFS), overall survival (OS), and frequency of complications of CW implantation (brain edema, infection, and cerebrospinal fluid leakage) were compared between the CW and non-use groups. RESULTS: In total, 127 patients (75 in the CW use group and 52 in the non-use group) were enrolled. Regardless of stratification, no significant differences in PFS and OS were observed between the CW use and non-use groups. The frequency of postoperative brain edema was significantly higher in the CW use group than in the non-use group. An adjusted dataset containing 41 patients in the CW use and nonuse groups was generated. Even after PSM, CW implantation had no prognostic effect. CONCLUSIONS: CW implantation with standard treatment demonstrated little beneficial effect for the present strategy of CW use.

A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study.

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

Drug release profile of a novel exenatide long-term drug delivery system (OKV-119) administered to cats.

Beneficial weight-loss properties of glucagon-like peptide-1 receptor agonists (GLP-1RA) in obese people, with corresponding improvements in cardiometabolic risk factors, are well established. OKV-119 is an investigational drug delivery system that is being developed for the long-term delivery of the GLP-1RA exenatide to feline patients. The purpose of this study was to evaluate the drug release characteristics of subcutaneous OKV-119 implants configured to release exenatide for 84 days. Following a 7-day acclimation period, five purpose-bred cats were implanted with OKV-119 protypes and observed for a 112-day study period. Food intake, weekly plasma exenatide concentrations and body weight were measured. Exenatide plasma concentrations were detected at the first measured timepoint (Day 7) and maintained above baseline for over 84 Days. Over the first 28 days, reduced caloric intake and a reduction in body weight were observed in four of five cats. In these cats, a body weight reduction of at least 5% was maintained throughout the 112-day study period. This study demonstrates that a single OKV-119 implant can deliver the GLP-1RA exenatide for a months long duration. Results suggest that exposure to exenatide plasma concentrations ranging from 1.5 ng/ml to 4 ng/ml are sufficient for inducing weight loss in cats.

Mobilizing stakeholders for implant removals in Burkina Faso using landscape assessment data.

BACKGROUND: Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal services are available when desired. In Burkina Faso, implant use has tripled over the past 8 years and now comprises almost half of the contraceptive method mix. Population Monitoring for Action (PMA) surveys identified barriers to obtaining quality removal when desired, particularly when the implant is not palpable, or providers lack needed skills or supplies. The Expanding Family Planning Choices (EFPC) project supported ministries of health in four countries with evaluation and strengthening of implant removal services. METHODS: An implant removal landscape assessment was conducted at 24 health facilities in three regions of Burkina Faso with high implant use that included provider observations of implant removal, interviews with providers and health facility managers, and facility readiness surveys. The project used landscape data to mobilize stakeholders through a series of participatory workshops to develop a collaborative roadmap and commit to actions supporting quality implant removals. RESULTS: Landscape findings revealed key gaps in provision of quality removal services, including high levels of provider confidence for implant insertion and removal (82% and 71%, respectively), low competence performing simple and difficult removals (19.2% and 11.1%, respectively), inadequate supplies and equipment (no facilities had all necessary materials for removal), lack of difficult removal management systems, and a lack of standard data collection tools for removal. Exposure to the data convinced stakeholders to focus on removals rather than expanding insertion services. While not all roadmap commitments were achieved, the process led to critical investments in quality implant removals. CONCLUSION: Landscape data revealed that facilities lack needed supplies and equipment, and providers lack skills needed to perform quality implant removals, limiting client reproductive choice. Disseminating this data enabled stakeholders to identify and commit to evidence-based priority actions. Stakeholders have since capitalized on program learnings and the roadmap, including following MOH guidance for implant removal supplies and health provider training. Our experience in Burkina Faso offers a replicable model of how data can direct collective action to improve quality of contraceptive implant removals.

DEXAMETHASONE IMPLANT VERSUS TOPICAL CARBONIC ANHYDRASE INHIBITORS IN PATIENTS WITH BILATERAL RETINITIS PIGMENTOSA-RELATED CYSTOID MACULAR EDEMA: A Prospective, Paired-Eye Pilot Study.

PURPOSE: To compare within-subject efficacy and safety of intravitreal dexamethasone implant and topical carbonic anhydrase inhibitors in the treatment of retinitis pigmentosa-related cystoid macular edema. METHODS: Patients with bilateral retinitis pigmentosa-related cystoid macular edema were treated with intravitreal dexamethasone implant in one eye and topical carbonic anhydrase inhibitors in the contralateral eye. The primary endpoint was a change in central macular thickness. Secondary endpoints were changes in best-corrected visual acuity and microperimetric central retinal sensitivity. Intraocular pressure and other ocular complications were evaluated for safety assessment. RESULTS: Nine patients were recruited for this 12-month follow-up study. Central macular thickness was significantly lower in intravitreal dexamethasone implant-treated eyes than in topical carbonic anhydrase inhibitors-treated eyes at Months 1 and 7, whereas mean best-corrected visual acuity was better in eyes treated with topical carbonic anhydrase inhibitors at Month 12 (borderline significant P = 0.0510). There was no difference in microperimetric sensitivity between the two treatments. Three patients developed ocular hypertension after intravitreal dexamethasone implant. Intravitreal dexamethasone implant showed an effect on the contralateral eye in five of nine patients. CONCLUSION: Intravitreal dexamethasone implant was more effective than topical carbonic anhydrase inhibitors in reducing retinitis pigmentosa-related cystoid macular edema 1 month after treatment. Corticosteroids can play a key role in the management of retinitis pigmentosa-related cystoid macular edema; however, their routes, timing, and modes of administration should be further explored.

A case of accidental into-the-lens dexamethasone implant: watching or removing?

BACKGROUND: To report a case of cataract surgery in unintentional Ozurdex (Allergan, Inc., Irvine, California, USA) injection into the lens. CASE PRESENTATION: A 82-years old man reporting decreased visual acuity in his right eye came to our Ophthalmology service. Due to the clinical history, and on the basis of ophthalmoscopic and imaging examinations diabetic macular edema was diagnosed. Thus, intravitreal dexamethasone implant was scheduled and therefore performed. The following day Ozurdex appeared to be located into the lens. After careful evaluation and strict follow up examinations, due to the risks associated with the presence of the implant into the lens, phacoemulsification with Ozurdex removal and intraocular lens (IOL) implantation was scheduled and performed. CONCLUSIONS: In this case report we reported the surgical management of accidental into-the lens dexamethasone implant carefully taking into account the dexamethasone pharmacokinetic.

Short-term effect of intravitreal dexamethasone implant in refractory diabetic macular edema.

PURPOSE: To evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections. METHODS: This was a prospective, single-arm, interventional clinical series. Eyes with DME and 3-9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA. RESULTS: Fifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003). CONCLUSIONS: Eyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT05736081 . Registered 20 February 2023, Retrospectively registered.

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

Offering extended use of the contraceptive implant via an implementation science framework: a qualitative study of clinicians' perceived barriers and facilitators.

BACKGROUND: The etonogestrel contraceptive implant is currently approved by the United States Food and Drug Administration (FDA) for the prevention of pregnancy up to 3 years. However, studies that suggest efficacy up to 5 years. There is little information on the prevalence of extended use and the factors that influence clinicians in offering extended use. We investigated clinician perspectives on the barriers and facilitators to offering extended use of the contraceptive implant. METHODS: Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured qualitative interviews. Participants were recruited from a nationwide survey study of reproductive health clinicians on their knowledge and perspective of extended use of the contraceptive implant. To optimize the diversity of perspectives, we purposefully sampled participants from this study. We used content analysis and consensual qualitative research methods to inform our coding and data analysis. Themes arose deductively and inductively. RESULTS: We interviewed 20 clinicians including advance practice clinicians, family medicine physicians, obstetrician/gynecologist and complex family planning sub-specialists. Themes regarding barriers and facilitators to extended use of the contraceptive implant emerged. Barriers included the FDA approval for 3 years and clinician concern about liability in the context of off-label use of the contraceptive implant. Educational materials and a champion of extended use were facilitators. CONCLUSIONS: There is opportunity to expand access to extended use of the contraceptive implant by developing educational materials for clinicians and patients, identifying a champion of extended use, and providing information on extended use prior to replacement appointments at 3 years.

Modeling programmable drug delivery in bioelectronics with electrochemical actuation.

Drug delivery systems featuring electrochemical actuation represent an emerging class of biomedical technology with programmable volume/flowrate capabilities for localized delivery. Recent work establishes applications in neuroscience experiments involving small animals in the context of pharmacological response. However, for programmable delivery, the available flowrate control and delivery time models fail to consider key variables of the drug delivery system--microfluidic resistance and membrane stiffness. Here we establish an analytical model that accounts for the missing variables and provides a scalable understanding of each variable influence in the physics of delivery process (i.e., maximum flowrate, delivery time). This analytical model accounts for the key parameters--initial environmental pressure, initial volume, microfluidic resistance, flexible membrane, current, and temperature--to control the delivery and bypasses numerical simulations allowing faster system optimization for different in vivo experiments. We show that the delivery process is controlled by three nondimensional parameters, and the volume/flowrate results from the proposed analytical model agree with the numerical results and experiments. These results have relevance to the many emerging applications of programmable delivery in clinical studies within the neuroscience and broader biomedical communities.

Migration of etonogestrel subcutaneous contraceptive implants: systematic review and recommendations for practice.

INTRODUCTION: Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. PURPOSE: To document and characterise cases of etonogestrel contraceptive implant migration in the scientific literature. METHODS: A systematic review of Medline, Embase and Global Health databases was carried out between January 2000 and January 2023 to identify articles presenting implant migrations. Narrative reviews, conference abstracts and articles not written in English or French were excluded. RESULTS: Forty-five articles, mostly published since 2016, were identified (eight case series and 37 case reports), for a total of 148 independent cases of migration: in pulmonary blood vessels (n = 74), in non-pulmonary blood vessels (n = 16) and extravascular (n = 58). Many patients are asymptomatic and migration is often an incidental finding. A non-palpable implant and symptoms related to implant location (intra- or extra-vascular) may be indicative of migration. Inadequate insertion and normal or underweight appear to increase the risk of migration. Scientific societies and authors offer practical strategies to deal with implant migration. CONCLUSION: Professionals who insert and remove contraceptive implants must be adequately trained. They need to be on the lookout for implant migration, and promptly refer patients to appropriate care if migration is suspected.

This systematic review documents and characterises 148 cases of vascular and extravascular etonogestrel contraceptive implant migration. Healthcare professionals must be aware of this rare but serious complication and be adequately trained to insert and remove contraceptive implants.

Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Wurster Technology-Assisted Step-by-Step Engineering of Multi-layered Pellets (Sprinkles): Microscopy, Micro-CT, and e-Tongue-Based Analysis.

The advancement in the formulation and characterization techniques have paved the path for development of new as well as modification of existing dosage forms. The present work explores the role of micro-computed tomography (micro-CT) as advanced characterization technique for multi-layered-coated pellets to ascertain the quality of coated pellets. The work further explored in-house e-tongue technique for understanding palatability of formulation in early stages of development thus by reducing clinical taste evaluation time. The developed multi-layered-coated pellets were characterized using microscopy (optical and electron microscopy). The obtained results demonstrated formation of spherical-shaped pellets with uniform coating. The uniform coating was further confirmed by results obtained from scanning electron microscopy (SEM) and cross-sectional SEM analysis, which showed visible difference in pellet surface before and after multi-layered coating. The micro-CT results confirmed the visible demarcation of layers (drug and polymer, i.e., hydroxypropyl methylcellulose (HPMC) and eudragit (EPO)) along with uniform thickness of various layering. The dissolution study of developed pellets suggested the role of layering EPO on drug release from pellets. The e-tongue analysis proved to be an excellent tool for early prediction of taste masking of drug via multi-layered pellets and can serve as potential platform for taste masking with high specificity. The overall results suggest the suitability of developed multi-layered platform as efficient dosage form (sprinkle) in pediatric/geriatric product development.

PILOT STUDY OF INTRACOELOMIC TERBINAFINE IMPLANTS IN GREATER SIRENS (SIREN LACERTINA).

Chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) has been documented in greater sirens (Siren lacertina) in the wild and in the pet trade. This study evaluated the use of terbinafine-impregnated implants for chytridiomycosis prophylaxis in greater sirens exposed to Bd. Implants were placed intracoelomically in both control (blank implant, n = 4) and treatment (24.5 mg of terbinafine implant, n = 4) groups. Sirens were exposed to Bd zoospores via 24-h immersion bath at 1 and 2 mon postimplant placement. Blood was collected monthly for plasma terbinafine levels, and skin swabs were collected weekly for Bd quantitative PCR. Animals with terbinafine implants had detectable concentrations of plasma terbinafine ranging from 17 to 102 ng/ml. Only one terbinafine-implanted animal had a peak concentration above the published minimum inhibitory concentration for terbinafine against Bd zoospores (63 ng/ml); however, it is unknown how plasma terbinafine concentrations relate to concentrations in the skin. There was no difference between the two treatment groups in clinical signs or Bd clearance rate, and no adverse effects from implants were observed. These findings indicate using intracoelomic drug implants for drug delivery in amphibians is safe; however, terbinafine efficacy in preventing Bd chytridiomycosis in sirens remains unclear. Further investigation of the use of intracoelomic implants and identification of effective drugs and doses in other amphibian species against Bd and other infectious diseases is warranted, as this may provide a practical method for long-term drug delivery in wildlife.

Comparing ranibizumab, dexamethasone implant, and combined therapy for macular edema secondary to branch retinal vein occlusion: a clinical trial.

BACKGROUND: Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO). METHODS: This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups. RESULTS: At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections. CONCLUSION: Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications. TRIAL REGISTRATION INFORMATION: The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).

"Fabrication of pellets via extrusion-spheronization for engineered delivery of Famotidine through specialized straws for Paediatrics".

OBJECTIVE: A simple and efficient drug delivery device was designed, viz. specialized straw comprising of famotidine-loaded fast disintegrating pellets. SIGNIFICANCE: Pediatric dosage forms are designed and developed considering the palatability in children of all ages. This specialized straw was intended for pediatrics presenting with dysphagia or associated symptoms. METHODS: The pellets were formulated using an extruder spheronization technique incorporated with Kyron T-314 as a super disintegrant. These pellets were characterized for their micromeritic properties, disintegration, and in vitro drug release. The specialized straw was evaluated for various parameters like flow rate of water siphoned through the straw and solvation volume. RESULTS: Pellets were found to have excellent flow properties, disintegration time was found to be 25-30s, and dissolution studies showed 96.1% drug release in 45min. In vitro flow rate was determined to simulate sipping action through this specialized straw. The results indicated that water flowing through the hollow straw at the rate of 13.8±1.3 mLs-1, when tested in prefilled specialized straw, 6.3±1.1 mLs-1 flow rate was observed to be sufficient to dissolve the pellets. CONCLUSION: Finally, the fast-disintegrating pellets demonstrated excellent in vitro performance and relative ease of manufacturing as compared to other solid dosage forms. Furthermore, the developed specialized straw can be used as a convenient and attractive drug delivery device for pediatrics.

Trends in Histrelin Implantation at a Pediatric Tertiary Care Center.

INTRODUCTION: Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over 15 y. METHODS: Retrospective review of all patients undergoing histrelin implantation between January 2008 and April 2022. RESULTS: A total of 746 patients underwent 1794 unique procedures (1364 placements/replacements, 430 removals). Procedures were performed in the clinic (1071, 60%), sedation unit (630, 35%), and operating room (93, 5%). A total of 14 (0.8%) complications were identified, including two patients that required early implant removal and one patient requiring antibiotics. Implants were placed for central precocious puberty (CPP, 579) or gender dysphoria (GD, 167). Cohort included 25.9% males and 74.1% females with mean age of implantation of 9.48 y (SD: 2.34, range: 1.05-17.34). The GD group is comprised of 52.4% males and 47.6% females, compared to 18.3% males and 81.7% females in the CPP. Significant difference was identified for mean age at placement by indication (CPP 8.65 y versus GD 12.34, P < 0.001). New patient referrals and implant procedures increased significantly over 14 y. Yearly frequency of patients receiving implants for CPP and GD increased significantly (P < 0.001), with proportion of GD patients increasing from 7% to 32%. CONCLUSIONS: Histrelin procedures have increased in frequency overall with the greater increase noted in the GD cohort. The development of a streamlined process and a dedicated team have enabled histrelin procedures to be safely performed in the clinic setting for most, with a very low complication rate.

Unexpected long-term retention of subcutaneous beeswax implants and additional notes on dose and composition from four testosterone implant studies.

Experimental manipulations of testosterone have advanced our understanding of the hormonal control of traits across vertebrates. Implants are commonly used to supplement testosterone and other hormones to organisms, as they can be readily scaled to produce desired hormone levels in circulation. Concerns about pharmacological (i.e. unnatural) doses of traditional silastic implants led to innovation in implant methods, with time-release pellets and beeswax implants proposed as solutions. A study comparing silastic, time-release pellets, and beeswax implants found the latter to be most effective in delivering a physiologically relevant dose. One proposed advantage to subcutaneous beeswax implants is that they are expected to degrade within the body, thus removing the obligation to recapture implanted individuals in the field. However, few studies have reported on dosage and no published literature has examined the assumption that beeswax implants readily degrade as expected. Here we present time-release androgen data in relation to implants containing varying levels of testosterone from four separate implant studies. In addition, we report long-term persistence of subcutaneous implants, including two cases of implants being retained for > 2 years. Finally, we offer recommendations on the composition and implementation of beeswax implants to aid the pursuit of minimally invasive and physiologically relevant manipulations of circulating hormones.

Fluocinolone acetonide 0.19-mg implant for the treatment of noninfectious uveitis with involvement of the posterior segment: a real-world study.

PURPOSE: To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi. METHODS: A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation. RESULTS: In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: - 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 µm, difference 53.57 µm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference - 1.92; 95% CI: - 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted. CONCLUSION: We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity.