-
Journal of Controlled Release :... Mar 2022The aim of this study was to better understand to which extent and in which way the presence of an agarose gel (mimicking living tissue) around a PLGA...
The aim of this study was to better understand to which extent and in which way the presence of an agarose gel (mimicking living tissue) around a PLGA [poly(lactic-co-glycolic acid)] implant affects the resulting drug release kinetics. Ibuprofen-loaded implants were prepared by hot melt extrusion. Drug release was measured upon exposure to phosphate buffer pH 7.4 in Eppendorf tubes, as well as upon inclusion into an agarose gel which was exposed to phosphate buffer pH 7.4 in an Eppendorf tube or in a transwell plate. Dynamic changes in the implants' dry & wet mass and dimensions were monitored gravimetrically and by optical macroscopy. Implant erosion and polymer degradation were observed by SEM and GPC. Different pH indicators were used to measure pH changes in the bulk fluids, gels and within the implants during drug release. Ibuprofen release was bi-phasic in all cases: A zero order release phase (~20% of the dose) was followed by a more rapid, final drug release phase. Interestingly, the presence of the hydrogel delayed the onset of the 2nd release phase. This could be attributed to the sterical hindrance of implant swelling: After a certain lag time, the degrading PLGA matrix becomes sufficiently hydrophilic and mechanically instable to allow for the penetration of substantial amounts of water into the system. This fundamentally changes the conditions for drug release: The latter becomes much more mobile and is more rapidly released. A gel surrounding the implant mechanically hinders system swelling and, thus, slows down drug release. These observations also strengthen the hypothesis of the "orchestrating" role of PLGA swelling for the control of drug release and can help developing more realistic in vitro release set-ups.
Topics: Drug Implants; Drug Liberation; Ibuprofen; Phosphates; Polylactic Acid-Polyglycolic Acid Copolymer; Sepharose
PubMed: 35085697
DOI: 10.1016/j.jconrel.2022.01.028 -
International Journal of Pharmaceutics May 2024In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis...
In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible solvent. The drug is dissolved or dispersed in this solution. Upon contact with aqueous body fluids, the solvent diffuses into the surrounding tissue and water penetrates into the formulation. Consequently, PLGA precipitates, trapping the drug. Often, N-methyl-2-pyrrolidine (NMP) is used as a water-miscible solvent. However, parenteral administration of NMP raises toxicity concerns. The aim of this study was to identify less toxic alternative solvent systems for in-situ forming PLGA implants. Various blends of polyethylene glycol 400 (PEG 400), triethyl citrate (TEC) and ethanol were used to prepare liquid formulations containing PLGA, ibuprofen (as an anti-inflammatory drug) and/or chlorhexidine dihydrochloride (as an antiseptic agent). Implant formation and drug release kinetics were monitored upon exposure to phosphate buffer pH 6.8 at 37 °C. Furthermore, the syringeability of the liquids, antimicrobial activity of the implants, and dynamic changes in the latter's wet mass and pH of the release medium were studied. Importantly, 85:10:5 and 60:30:10 PEG 400:TEC:ethanol blends provided good syringeability and allowed for rapid implant formation. The latter controlled ibuprofen and chlorhexidine release over several weeks and assured efficient antimicrobial activity. Interestingly, fundamental differences were observed concerning the underlying release mechanisms of the two drugs: Ibuprofen was dissolved in the solvent mixtures and partially leached out together with the solvents during implant formation, resulting in relatively pronounced burst effects. In contrast, chlorhexidine dihydrochloride was dispersed in the liquids in the form of tiny particles, which were effectively trapped by precipitating PLGA during implant formation, leading to initial lag-phases for drug release.
Topics: Polylactic Acid-Polyglycolic Acid Copolymer; Solvents; Ibuprofen; Drug Liberation; Polyethylene Glycols; Drug Implants; Polyglycolic Acid; Chlorhexidine; Lactic Acid; Citrates; Ethanol
PubMed: 38621617
DOI: 10.1016/j.ijpharm.2024.124121 -
Journal of Pediatric and Adolescent... Jun 2022To describe clinical outcomes in a cohort of adolescent female patients using tamoxifen for the treatment of bothersome etonogestrel (ENG) implant-associated bleeding.
OBJECTIVE
To describe clinical outcomes in a cohort of adolescent female patients using tamoxifen for the treatment of bothersome etonogestrel (ENG) implant-associated bleeding.
DESIGN
Retrospective chart review SETTING: A tertiary children's hospital PARTICIPANTS: Adolescent female patients ages 12-21 seen between August 2016 and August 2019 with an ENG implant in place who received a tamoxifen prescription for the indication of implant-associated bleeding.
INTERVENTIONS
None MAIN OUTCOME MEASURES: Main outcome measures were implant continuation rates, average time to implant discontinuation after tamoxifen prescription, reasons for implant removal, number of doses and timing of tamoxifen use, bleeding patterns, and adverse effects.
RESULTS
A total of 67 patients met the inclusion criteria. The mean age of patients was 16.7 years old. Of the patients with available follow-up data, 49 out of 60 (81.7%) were still using the implant at 12 months, 29 out of 53 (54.7%) at 24 months, and 9 out of 40 (22.5%) at 36 months. The average time from tamoxifen prescription to implant removal was 12.1 months. Bothersome bleeding was the primary reason for ENG implant discontinuation (68.6%). No side effects from tamoxifen use were reported.
CONCLUSION
Tamoxifen was well-tolerated among this cohort of patients and can be considered a treatment option to manage bothersome implant bleeding in adolescents.
Topics: Adolescent; Adult; Child; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Gynecology; Hemorrhage; Humans; Retrospective Studies; Tamoxifen; Young Adult
PubMed: 34780932
DOI: 10.1016/j.jpag.2021.11.001 -
The Journal of Surgical Research Nov 2023Determine procedural outcomes and identify changing trends of utilization among patients undergoing histrelin implantation at a large pediatric tertiary care center over...
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.
Topics: Male; Female; Humans; Child; Tertiary Care Centers; Drug Implants; Gonadotropin-Releasing Hormone; Puberty, Precocious; Retrospective Studies
PubMed: 37352739
DOI: 10.1016/j.jss.2023.05.019 -
Daru : Journal of Faculty of Pharmacy,... Dec 2020Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for...
AIM
Liqui-Pellet is potentially an emerging next-generation oral pill, which has shown promising results with unique advantages as well as displaying potential for commercial feasibility. Since Liqui-Pellet technology is still in its infancy, it is important to explore the parameters that can affect its performance, particularly the drug release rate. Therefore, the aim of this study is to investigate thoroughly the effect of Avicel PH101 (carrier) and Aerosil 300 (coating material) ratio (R-value) in Liqui-Pellet.
METHODS
Key parameter for Liqui-Pellet formulation in this study was the ratio of carrier and coating material. Tests were carried out to assess the physicochemical properties of different formulations. This involved looking into particle size, robustness, flowability, solid-state and drug release profile. The morphology of Liqui-Pellet was investigated by SEM.
RESULTS
It is found that R-value does not have a major effect on the success of Liqui-Pellet production. However, R-value does seem to have an effect on Liqui-Pellet size at a certain water content level and a slight effect on the drug release rate. A decrease in Avicel PH101 concentration and an increase in Aerosil 300 concentration in Liqui-Pellet formulations can reduce Liqui-Pellet size and slightly increase drug release rate by 9% after 2 h. The data shows Liqui-Pellet is resistant to friability, able to achieve exceptional flow property and have smooth surfaces, which is critical for applying coatings technology. Such properties are ideal in terms of commercial manufacturing. The XRPD and DSC both show the reduction in formulation crystallinity, which is expected in Liqui-Pellet formulation as a result of solubility of the drug in the co-solvent used in the preparation of Liqui-Pellets.
CONCLUSION
Overall it seems that R-value can affect Liqui-Pellet drug release rate and size but not on the production success rate.
Topics: Calorimetry, Differential Scanning; Cellulose; Drug Compounding; Drug Implants; Microscopy, Electron, Scanning; Naproxen; Particle Size; Powder Diffraction; Silicon Dioxide; Solubility; X-Ray Diffraction
PubMed: 32757155
DOI: 10.1007/s40199-020-00362-9 -
International Journal of Pharmaceutics Apr 2023Intravitreal injections are the preferred choice for drug administration to the posterior segment of the eye. However, the required frequent injections may cause...
Intravitreal injections are the preferred choice for drug administration to the posterior segment of the eye. However, the required frequent injections may cause complications to the patient and low adherence to the treatment. Intravitreal implants are able to maintain therapeutic levels for a long period. Biodegradable nanofibers can modulate drug release and allow the incorporation of fragile bioactive drugs. Age-related macular degeneration is one of the world major causes of blindness and irreversible vision loss. It involves the interaction between VEGF and inflammatory cells. In this work we developed nanofiber-coated intravitreal implants containing dexamethasone and bevacizumab for simultaneously delivery of these drugs. The implant was successfully prepared and the efficiency of the coating process was confirmed by scanning electron microscopy. Around 68% of dexamethasone was released in 35 days and 88% of bevacizumab in 48hs. The formulation presented activity in the reduction of vessels and was safe to the retina. It was not observed any clinical or histopathological change, neither alteration in retina function or thickness by electroretinogram and optical coherence tomography during 28 days. The nanofiber-coated implants of dexamethasone and bevacizumab may be considered as a new delivery system that can be effective for the treatment of AMD.
Topics: Animals; Rabbits; Bevacizumab; Glucocorticoids; Dexamethasone; Nanofibers; Drug Implants; Intravitreal Injections; Angiogenesis Inhibitors; Treatment Outcome
PubMed: 36894043
DOI: 10.1016/j.ijpharm.2023.122809 -
Retina (Philadelphia, Pa.) Aug 2023To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients...
PURPOSE
To assess the efficacy of a 0.18 mg intravitreal fluocinolone acetonide (FA) implant (Yutiq, EyePoint Pharmaceuticals, Watertown, MA) as a treatment option for patients with radiation retinopathy-related cystoid macular edema.
METHODS
A retrospective review of seven patients treated for uveal melanoma who developed radiation retinopathy-related cystoid macular edema. They were initially treated with intravitreal anti-vascular endothelial growth factor and/or steroid injections and then transitioned to intravitreal FA implant. Primary outcomes include best-corrected visual acuity, central subfield thickness, and number of additional injections.
RESULTS
After FA implant insertion, best-corrected visual acuity and central subfield thickness remained stable in all patients. The variance in best-corrected visual acuity decreased from 75.5 ETDRS letters (range 0-199 letters) to 29.8 (range 1.2-134) after FA implant insertion. Mean central subfield thickness was 384 µ m (range 165-641) and 354 µ m (range 282-493) before and after FA implant insertion, resulting in a 30- µ m mean reduction. The number of intravitreal injections (average 4.9, range 2-10) decreased after intravitreal FA implant insertion with only two patients requiring one additional FA implant (average 0.29, range 0-1) over a mean of 12.1 months (range 0.9-18.5) follow-up.
CONCLUSION
Intravitreal FA implant is an effective treatment for cystoid macular edema radiation retinopathy. The slow release of steroid allows for sustained control of macular edema, which correlated with stable visual acuity and decreased injection burden for patients.
Topics: Humans; Glucocorticoids; Macular Edema; Diabetic Retinopathy; Drug Implants; Fluocinolone Acetonide; Retrospective Studies; Intravitreal Injections
PubMed: 37027785
DOI: 10.1097/IAE.0000000000003808 -
European Journal of Ophthalmology May 2021The purpose of this study was to determine the effects of dexamethasone implant (0.7 mg) on biomarkers such as hyper-reflective dots, external limiting membrane...
PURPOSE
The purpose of this study was to determine the effects of dexamethasone implant (0.7 mg) on biomarkers such as hyper-reflective dots, external limiting membrane integrity and disorganization of retinal inner layers in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases with diabetic macular edema and its effects on edema and visual acuity.
METHODS
This is a prospective study of treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder patients with diabetic macular edema, treated with single dexamethasone implant. Pre- and post-injection-based best-corrected visual acuity, central macular thickness, hyper-reflective dots, external limiting membrane integrity and disorganization of retinal inner layers were assessed.
RESULTS
A total of 27 diabetic macular edema eyes, including 9 non-responder eyes, 9 eyes which received less than three anti-vascular endothelial growth factor injections and 9 treatment-naïve eyes, were included in this study. Baseline hyper-reflective dots were 22.22 ± 11.76, 30 ± 7.91 and 19.44 ± 8.82 which reduced to 3.33 ± 1.32, 9 ± 8.35 and 8.78 ± 2.53 four months after implant in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases, respectively. Baseline central macular thickness was 589.44 ± 175.37, 537 ± 181.81 and 673.11 ± 138.24 and the central macular thickness after dexamethasone implant was 272.11 ± 39.00, 336.44 ± 132.88 and 524.00 ± 200.39 in treatment-naïve patients, patients who received less than three anti-vascular endothelial growth factor injections and non-responder cases, respectively. External limiting membrane integrity was restored in two patients in each group, whereas two patients with disorganization of retinal inner layers in treatment-naïve group showed reorganization of retinal structures after treatment with dexamethasone implant.
CONCLUSION
Better response to dexamethasone implant in cases with more hyper-reflective dots shows that these hyper-reflective dots can be used as a predictive biomarker. Dexamethasone implant might help in restoring external limiting membrane integrity and resolution of disorganization of retinal inner layers.
Topics: Angiogenesis Inhibitors; Biomarkers; Dexamethasone; Diabetes Mellitus; Diabetic Retinopathy; Drug Implants; Glucocorticoids; Humans; Intravitreal Injections; Macular Edema; Prospective Studies; Retrospective Studies; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A
PubMed: 32429696
DOI: 10.1177/1120672120925788 -
Molecules (Basel, Switzerland) Dec 2022This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific...
This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific medication delivery for the potential treatment of colorectal cancer. Six polymer-based formulations were successfully produced using a thermal bulk polymerization method and loaded with 5-fluorouracil, which is a chemotherapeutic agent used in the treatment of colorectal carcinoma. The pellets produced were characterized by measuring the glass transition temperature, tensile strength, Young's modulus, and tensile elongation at break. Studies on in vitro swelling and release were carried out in phosphate-buffered saline to evaluate the behaviour of the developed system. The Young's modulus, glass transition temperature, and tensile strength all increased significantly as the crosslinker concentration increased, but the fracture strain value reduced significantly. The in vitro swelling profile of the produced formulations was significantly reduced by increasing crosslinking density. Less than 27% cumulative drug release was achieved for all formulations after 5 h of starting the release study. The highest cumulative drug release reached after 24 h was 69%. The developed drug delivery system demonstrated the ability to delay the release of 5-fluorouracil in upper gastrointestinal tract-mimicking conditions, while permitting its release in a controlled way afterward, which makes it promising for the potential delivery of 5-fluorouracil to the colon.
Topics: Fluorouracil; Drug Delivery Systems; Drug Implants; Polymers; Colon
PubMed: 36615499
DOI: 10.3390/molecules28010306 -
The European Journal of Contraception &... Jun 2024Migration is a rare but serious complication of the etonogestrel contraceptive implant, and little is known about its extent. (Review)
Review
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 ( = 74), in non-pulmonary blood vessels ( = 16) and extravascular ( = 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.
Topics: Humans; Desogestrel; Foreign-Body Migration; Female; Drug Implants; Contraceptive Agents, Female; Device Removal; Contraceptive Agents, Hormonal
PubMed: 38712717
DOI: 10.1080/13625187.2024.2342919