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General and Comparative Endocrinology Oct 2022Transmasculine individuals are often prescribed testosterone (T) for masculinizing hormone therapy. Mouse models mimicking transmasculine T therapy require reliable...
Transmasculine individuals are often prescribed testosterone (T) for masculinizing hormone therapy. Mouse models mimicking transmasculine T therapy require reliable long-term T administration. The objectives of this study were three-fold, namely, to compare: 1) the release dynamics of three different subcutaneous delivery systems of T enanthate administration (subcutaneous injections, commercially available pellets, and silastic implants) over a 6-week period in postpubertal C57BL/6N mice, 2) to compare the timing for T levels in plasma to return to baseline and cyclicity to resume after cessation of T between injections and pellets, 3) to utilize silastic implants to achieve sustainable increase in T levels utilizing T enanthate and crystalline T. All three modes of T administration resulted in an increase in T levels in plasma. Pharmacokinetic analyses showed a similar overall exposure to T enanthate over 6 weeks (integrated area) for, subcutaneous injection (0.45 mg two times per week and 0.90 mg one time per week), pellet (5 mg 60-day release), and silastic implant (5 mg 21 week) groups. Crystalline T had lower solubility and a decreased integrated area compared to T enanthate, even when implanted at a higher dosage, indicating different pharmacokinetic profiles based on type of T formulation when utilizing the same silastic delivery method. Surgical removal of pellets and silastic tubing led to a quick drop in T levels and resumption of estrous cyclicity, while cessation of injections required a long washout period for T levels to drop and estrous cycles to resume. Sustained elevation in T levels was achieved for at least 21 weeks with silastic implants. As all three delivery methods are able to elevate T levels in female mice for at least 6 weeks, choice of T administration method should be based on outcomes of interest and study design.
Topics: Animals; Drug Implants; Female; Heptanoates; Injections, Subcutaneous; Mice; Mice, Inbred C57BL; Testosterone
PubMed: 35753388
DOI: 10.1016/j.ygcen.2022.114090 -
International Journal of Pharmaceutics Mar 2024The influences of the punch face design on multi-unit pellet system (MUPS) tablets were investigated. Drug-loaded pellets coated with sustained release polymer based on...
The influences of the punch face design on multi-unit pellet system (MUPS) tablets were investigated. Drug-loaded pellets coated with sustained release polymer based on ethylcellulose or acrylic were compacted into MUPS tablets. Punch face designs used include standard concave, deep concave, flat-faced bevel edge and flat-faced radius edge. MUPS tablets compacted at 2 or 8 kN were characterized for their tensile strength. The extent of pellet coat damage after tableting was evaluated from drug release profiles. Biconvex tablets were weaker by 0.01-0.15 MPa, depending on the pellet type used, and had 1-17 % higher elastic recovery (p < 0.000) than flat-faced tablets. At higher compaction force, the use of the deep concave punch showed a 13-26 % lower extent of pellet coat damage, indicated by a relatively higher mean dissolution time, compared to other punch face configurations (p < 0.000). This was attributed to increased rearrangement energy of the compacted material due to the high punch concavity, which sequestered compaction stress exerted on pellet coats. Although the deep concave punch reduced the stress, the resultant tablets containing pellets coated with acrylic were weaker (p = 0.01). Overall, the punch face configuration significantly affected the quality of MUPS tablets.
Topics: Drug Compounding; Excipients; Drug Implants; Polymers; Drug Liberation; Tablets; Tensile Strength
PubMed: 38307400
DOI: 10.1016/j.ijpharm.2024.123863 -
European Journal of Ophthalmology Nov 2021To analyse the morpho-functional outcomes of dexamethasone intravitreal implant (Ozurdex) injected after lens surgery in diabetic patients with coexisting cataract and...
PURPOSE
To analyse the morpho-functional outcomes of dexamethasone intravitreal implant (Ozurdex) injected after lens surgery in diabetic patients with coexisting cataract and macular oedema.
METHODS
This is a non-randomized, perspective, single-group study on 17 eyes with a diagnosis of cataract and early and advanced diabetic macular oedema. All eyes underwent combined phacoemulsification and Ozurdex injection at the end of surgery and morpho-functional outcomes were analysed in 3 months follow-up.
RESULTS
Foveal thickness decreased significantly from 349.6 ± 19.8 (95% CI) at baseline to 310.7 ± 17.5 (95% CI) 90 days after surgery ( < 0.01).Mean BCVA (LogMAR) improved significantly from 0.38 ± 0.08 (95% CI) at baseline to 0.15 ± 0.06 (95% CI) after 90 days ( < 0.01). Any ocular or systemic complications were observed during follow-up.
CONCLUSIONS
Dexamethasone intravitreal implant combined with phacoemulsification may be safe and effective to improve morpho-functional outcomes in diabetic patients with coexisting cataract and macular oedema.
Topics: Dexamethasone; Diabetes Mellitus; Diabetic Retinopathy; Drug Implants; Glucocorticoids; Humans; Intravitreal Injections; Phacoemulsification; Visual Acuity
PubMed: 34382420
DOI: 10.1177/11206721211039347 -
Advanced Healthcare Materials Feb 2015Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In...
Primary or secondary hypogonadism results in a range of signs and symptoms that compromise quality of life and requires life-long testosterone replacement therapy. In this study, an implantable nanochannel system is investigated as an alternative delivery strategy for the long-term sustained and constant release of testosterone. In vitro release tests are performed using a dissolution set up, with testosterone and testosterone:2-hydroxypropyl-β-cyclodextrin (TES:HPCD) 1:1 and 1:2 molar ratio complexes release from the implantable nanochannel system and quantify by HPLC. 1:2 TES:HPCD complex stably achieve 10-15 times higher testosterone solubility with 25-30 times higher in vitro release. Bioactivity of delivered testosterone is verified by LNCaP/LUC cell luminescence. In vivo evaluation of testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels by liquid chromatography mass spectrometry (LC/MS) and multiplex assay is performed in castrated Sprague-Dawley rats over 30 d. Animals are treated with the nanochannel implants or degradable testosterone pellets. The 1:2 TES:HPCD nanochannel implant exhibits sustained and clinically relevant in vivo release kinetics and attains physiologically stable plasma levels of testosterone, LH, and FSH. In conclusion, it is demonstrated that by providing long-term steady release 1:2 TES:HPCD nanochannel implants may represent a major breakthrough for the treatment of male hypogonadism.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Drug Delivery Systems; Drug Implants; Follicle Stimulating Hormone; Kinetics; Luminescent Measurements; Luteinizing Hormone; Male; Nanostructures; Orchiectomy; Rats, Sprague-Dawley; Testosterone; beta-Cyclodextrins
PubMed: 25274059
DOI: 10.1002/adhm.201400348 -
Therapeutic Delivery Jun 2019Macular edema (ME) is the leading cause of visual loss in uveitis and may persist long after ocular inflammation has been resolved. Local steroids are the first line... (Review)
Review
Macular edema (ME) is the leading cause of visual loss in uveitis and may persist long after ocular inflammation has been resolved. Local steroids are the first line treatment for uveitis and uveitic ME. Dexamethasone intravitreal implant (OZURDEX; Allergan, Inc., CA, USA) has been used to treat diabetic ME and ME secondary to retinal vein occlusion. Recent studies have also demonstrated that Ozurdex may be effective treatment for patients with persistent uveitic ME. In this review, we present the results of the real word studies concerning the efficacy and safety of Ozurdex for the treatment of uveitic ME.
Topics: Cataract; Clinical Trials as Topic; Dexamethasone; Disease Progression; Drug Implants; Glucocorticoids; Humans; Intraocular Pressure; Intravitreal Injections; Macular Edema; Treatment Outcome; Uveitis
PubMed: 31184554
DOI: 10.4155/tde-2019-0024 -
Journal of Pharmaceutical Sciences Feb 2018To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing...
To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (e.g., withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage, and transport conditions), process design should include consideration of precise limits of accurate micro, macro, and bulk properties of the constituent pellets. This communication presents a comprehensive intricate database of micromechanical properties' and breakage probability distribution functions of pellets, illustrating the stiffening and strengthening effects of coatings and the softening and weakening effects of structural moisture. Further insights such as the (contact) history-dependent softening during decompression, strain hardening on repeated stressing, strength recovery by drying, and the fragmentation pattern by cracking are also presented. The contents herein are based on conveniently performable lab-scale diametrical compression measurements on model microcrystalline cellulose pellets-demonstrating feasibility of the approach and validity of the contribution.
Topics: Cellulose; Drug Compounding; Drug Implants; Excipients; Reproducibility of Results; Stress, Mechanical; Tensile Strength
PubMed: 28923319
DOI: 10.1016/j.xphs.2017.08.022 -
STAR Protocols Mar 2022Ocular drug implants (ODIs) are beneficial for treating ocular diseases. However, the lack of a robust injection approach for small-eyed model organisms has been a major...
Ocular drug implants (ODIs) are beneficial for treating ocular diseases. However, the lack of a robust injection approach for small-eyed model organisms has been a major technical limitation in developing ODIs. Here, we present a cost-effective, minimally invasive protocol to deliver ODIs into the mouse vitreous called Mouse Implant Intravitreal Injection (MI3). MI3 provides two alternative surgical approaches (air-pressure or plunger) to deliver micro-scaled ODIs into milli-scaled eyes, and expands the preclinical platforms to determine ODIs' efficacy, toxicity, and pharmacokinetics. For complete details on the use and execution of this protocol, please refer to Sun et al. (2021).
Topics: Animals; Drug Implants; Intravitreal Injections; Mice; Vitreous Body
PubMed: 35141566
DOI: 10.1016/j.xpro.2022.101143 -
Advanced Healthcare Materials Feb 2019Otitis media with effusion (OEM) is a common pediatric pathology treated with topical fluoroquinolones (ear drops) and tympanoplasty tube, also referred to as ear tube,...
Otitis media with effusion (OEM) is a common pediatric pathology treated with topical fluoroquinolones (ear drops) and tympanoplasty tube, also referred to as ear tube, implantation for middle ear drainage. Commercially available ear tubes are fabricated using poly (lactic-co-glycolic acid) synthetic materials that are associated with long-complications due to premature extrusion. Resorbable materials have emerged as desirable alternatives to reduce extrusion-related complications, but often limited by fast resorption rates. Therefore, resorbable tubes with long-term functional integrity are required for future clinical translation. In this communication, a proof-of-concept study is reported on a bioresorbable and drug-eluting silk ear tube device. Preliminary in vitro assessments reveal time-dependent drug elution and antimicrobial properties, while maintaining long-term functional integrity in vivo. This report provides evidence of a silk ear tube with potential for future clinical translation and OEM treatment.
Topics: Absorbable Implants; Animals; Anti-Bacterial Agents; Child; Chinchilla; Drug Implants; Fluoroquinolones; Humans; Otitis Media with Effusion; Silk; Time Factors; Tympanoplasty
PubMed: 30624860
DOI: 10.1002/adhm.201801409 -
Drug Development Research Nov 2019To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY-containing modified-release...
To minimize the gastric and esophageal injury effect, a system to deliver doxycycline hyclate (DOXY) to the duodenum area is needed. DOXY-containing modified-release oral pellets (DMOP) coated with hydroxypropyl methylcellulose phthalate HP-55 (HPMCP HP-55) and hydroxypropyl methylcellulose E15 (HPMC E15) appear to be a reasonable choice. This coating layer dissolves at pH 5.5, which is the pH of the duodenum, but not at a gastric pH (1.2). The formulation and preparation of DMOP were optimized, and a scale-up test was performed. The results showed that the production reproducibility was acceptable, and the quality of DMOP well met the standards of Chinese Pharmacopeia (Ch.P, 2015 edition). Notably, the accumulated DOXY release was lower than 50% at pH 1.2 (20 min) and higher than 85% at pH 5.5, which met the USP40-NF35 standard for DOXY modified-release formulations. Moreover, the storage stability of DMOP with different packages was investigated by stress testing, accelerated and long-term testings. The stability of DMOP was maintained up to 12 months, in terms of DOXY content and in vitro release behavior. The results seem to suggest that DMOP could be a promising duodenum delivery system.
Topics: Administration, Oral; Doxycycline; Drug Delivery Systems; Drug Implants; Drug Liberation; Drug Stability; Hydrogen-Ion Concentration; Hypromellose Derivatives; Methylcellulose; Particle Size; Tablets, Enteric-Coated
PubMed: 31359488
DOI: 10.1002/ddr.21575 -
AAPS PharmSciTech Feb 2015Self-emulsifying pellets were prepared using microcrystalline cellulose, emulsions of caprylic/capric triglyceride, and three Cremophors (ELP, RH40, and RH60) at 1.5 and...
Self-emulsifying pellets were prepared using microcrystalline cellulose, emulsions of caprylic/capric triglyceride, and three Cremophors (ELP, RH40, and RH60) at 1.5 and 2.3 weight ratios, and two drugs (furosemide and propranolol) of different lipophilicity. Droplet size, zeta potential (ζ) and viscosity of emulsions, and pellet size, shape, friability, tensile strength, disintegration, and drug migration in pellets were determined. Evaluation of reconstituted emulsions was based on droplet size and ζ. Factorial design and 3-way ANOVA was applied to estimate the significance of the effects of the drug, surfactant and oil/surfactant ratio. It was found that droplet size, viscosity and ζ of emulsions, and size, shape, and friability of pellets were affected by the studied factors and were significant interactions between their effects on pellet size and friability. Migration of drug towards the pellet surface was higher for the less lipophilic furosemide and higher oil content. Linear relationships were found between the emulsion viscosity and the shape parameters of the pellets (for the aspect ratio R (2) = 0.796 for furosemide and R (2) = 0.885 for propranolol and for the shape factor, e R R (2) = 0.740 and R (2) = 0.960, respectively). For all the formulations examined, an exponential relationship was found between migration (M%) and the product of viscosity (η) and solubility of drug in oil/surfactant mixture (S) (M% = 98.1e-0.016 [η•S], R (2) = 0.856), which may be useful in formulation work.
Topics: Absorption, Physicochemical; Diffusion; Drug Compounding; Drug Implants; Drug Stability; Emulsifying Agents; Emulsions; Furosemide; Particle Size; Propranolol; Tensile Strength; Viscosity
PubMed: 25212898
DOI: 10.1208/s12249-014-0214-8