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Contraception Jan 1997Safety, contraceptive efficacy and biodegradability of subdermal norethindrone (NET)-cholesterol implants (Anuelle) were investigated in 19 healthy, sexually active... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Safety, contraceptive efficacy and biodegradability of subdermal norethindrone (NET)-cholesterol implants (Anuelle) were investigated in 19 healthy, sexually active women. Mean serum NET levels in women with four and five pellets, containing 174 mg and 266.5 mg NET, showed a "burst-effect" of 3.17 and 3.71 ng/ml, respectively, within 24 h post implantation. Subsequently, for the four- and five-pellet groups, respectively, the levels declined from 0.75 to 0.40 ng/ml and 1.05 to 0.61 ng/ml during the months 12-15, from 0.40 to 0.11 ng/ml and 0.61 to 0.25 ng/ml up to month 36. The serum NET levels were undetectable at 36 months and beyond, indicating complete biodegradability of NET pellets. Serum E2 levels remained within normal limits (> 50 pg/ml), whereas serum P indicated anovulatory cycles in 78% of the four-pellet group and 99% of the five-pellet group. FSH and LH levels were subnormal and acyclic. Plasma lipids showed reduced total and LDL cholesterol and triglycerides. HDL cholesterol remained unchanged. Drug-related adverse effects were essentially limited to irregular bleeding. There were no pregnancies in either group.
Topics: Adolescent; Adult; Biodegradation, Environmental; Drug Implants; Female; Gonadal Steroid Hormones; Gonadotropins, Pituitary; Humans; Lipoproteins; Menstruation; Norethindrone; Patient Acceptance of Health Care; Progesterone Congeners
PubMed: 9013058
DOI: 10.1016/s0010-7824(97)00238-2 -
The AAPS Journal Sep 2010Osmotically controlled implants yield precise zero-order drug delivery kinetics and are utilized in a number of applications. The implants deliver drugs for extended... (Review)
Review
Osmotically controlled implants yield precise zero-order drug delivery kinetics and are utilized in a number of applications. The implants deliver drugs for extended periods (weeks to years) and exhibit good in vivo/in vitro correlation. This paper reviews critical variables associated with these implants, with a focus on release rate testing. The extended-duration kinetics can be problematic when attempting to test for >70% cumulative delivery. An innovative scheme based on the scientific principles of operation of the system is described to ensure > 70% delivery at the target rate and duration for the DUROS Viadur (leuprolide acetate) implant.
Topics: Drug Implants; Osmosis; Pharmacokinetics
PubMed: 20490735
DOI: 10.1208/s12248-010-9199-8 -
The Journal of Family Planning and... Oct 2006
Topics: Adult; Alopecia; Contraceptive Agents, Female; Desogestrel; Drug Implants; Female; Humans; Progestins
PubMed: 17032520
DOI: 10.1783/147118906778586435 -
Journal of Pharmaceutical Sciences Dec 2020Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors...
Continuous Manufacturing of Ketoprofen Delayed Release Pellets Using Melt Extrusion Technology: Application of QbD Design Space, Inline Near Infrared, and Inline Pellet Size Analysis.
Delayed-release dosage forms are mainly manufactured as batch processes and include coated tablets, pellets, or particles with gastric resistant polymers. Authors propose a novel approach using the hot-melt extrusion technique to prepare delayed release dosage forms via a continuous manufacturing process, a new trend in the pharmaceutical industry. A full factorial design was employed to correlate input variables, including stearic acid (SA) content, drug content, and pellet size with drug release properties of the pellets. PLS fit method suitably elaborated the relationship between input and output variables with reasonably good fit and goodness of prediction. All three input factors influenced drug release in enzyme-free simulated gastric fluid (SGF) after 120 min; however, SA content did not significantly affect drug dissolution in the enzyme-free simulated intestinal fluid (SIF). An optimized formulation and design space were determined by overlaying multiple contours established from regression equations. The continuous manufacturing process was successfully monitored using inline near-infrared (NIR) and inline particle size analysis, with drug load and pellet size being well-controlled within the design space. The obtained pellets released less than 5% after 120 min in SGF and more than 85% and 95% after 30 min and 45 min, respectively, after switching to SIF.
Topics: Drug Compounding; Drug Implants; Drug Liberation; Hot Melt Extrusion Technology; Ketoprofen; Particle Size; Solubility
PubMed: 32916139
DOI: 10.1016/j.xphs.2020.09.007 -
Drug Delivery Dec 2021Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and...
Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.
Topics: Animals; Anti-Bacterial Agents; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Implants; Drug Liberation; Microspheres; Minocycline; Osteoblasts; Osteogenesis; Osteoprotegerin; Periodontitis; Polylactic Acid-Polyglycolic Acid Copolymer; Rats; Rats, Sprague-Dawley; Receptor Activator of Nuclear Factor-kappa B; Sucrose
PubMed: 33779441
DOI: 10.1080/10717544.2021.1902020 -
Acta Biomaterialia Apr 2017A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications....
UNLABELLED
A persistent challenge in enhancing gene therapy is the transient availability of the target gene product. This is particularly true in tissue engineering applications. The transient exposure of cells to the product could be insufficient to promote tissue regeneration. Here we report the development of a new material engineered to have a high affinity for a therapeutic gene product. We focus on insulin-like growth factor-I (IGF-I) for its highly anabolic effects on many tissues such as spinal cord, heart, brain and cartilage. One of the ways that tissues store IGF-I is through a group of insulin like growth factor binding proteins (IGFBPs), such as IGFBP-5. We grafted the IGF-I binding peptide sequence from IGFBP-5 onto alginate in order to retain the endogenous IGF-I produced by transfected chondrocytes. This novel material bound IGF-I and released the growth factor for at least 30days in culture. We found that this binding enhanced the biosynthesis of transfected cells up to 19-fold. These data demonstrate the coordinated engineering of cell behavior and material chemistry to greatly enhance extracellular matrix synthesis and tissue assembly, and can serve as a template for the enhanced performance of other therapeutic proteins.
STATEMENT OF SIGNIFICANCE
The present manuscript focuses on the enhancement of chondrocyte gene therapy through the modification of scaffold materials to enhance the retention of targeted gene products. This study combined tissue engineering and gene therapy, where customized biomaterials augmented the action of IGF-I by enhancing the retention of protein produced by transfection of the IGF-I gene. This approach enabled tuning of binding of IGF-I to alginate, which increased GAG and HYPRO production by transfected chondrocytes. To our knowledge, peptide-based modification of materials to augment growth factor-targeted gene therapy has not been reported previously.
Topics: Animals; Biocompatible Materials; Cattle; Cells, Cultured; Chondrocytes; Drug Implants; Genetic Therapy; Insulin-Like Growth Factor I; Tissue Scaffolds; Transfection
PubMed: 28185909
DOI: 10.1016/j.actbio.2017.02.008 -
Medicine Jul 2017Controversies have been observed among network meta-analyses comparing biodegradable polymer drug-eluting stents (BP-DES) with durable polymer drug-eluting stents... (Meta-Analysis)
Meta-Analysis Review
Adverse cardiovascular events associated with biodegradable polymer drug-eluting stents and durable polymer everolimus-eluting stents: A systematic review and meta-analysis of 10 randomized controlled trials.
BACKGROUND
Controversies have been observed among network meta-analyses comparing biodegradable polymer drug-eluting stents (BP-DES) with durable polymer drug-eluting stents (DP-DES). We aimed to compare the adverse cardiovascular events associated with BP-DES and durable polymer everolimus-eluting stents (DP-EES) using a large number of patients obtained from randomized controlled trials (RCTs).
METHODS
Electronic databases were searched for randomized trials comparing BP-DES with DP-EES. Adverse cardiovascular outcomes observed between 6 months and 3 years were considered as the clinical endpoints in this analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software. All authors had full access to the data, and they have read and agreed to the manuscript as written.
RESULTS
Ten trials involving a total number of 13,218 patients (7451 patients treated by BP-DES and 5767 patients treated by DP-EES) were included. No significant difference was observed when analyzing mortality and myocardial infarction between BP-DES and DP-EES with OR 1.08, 95% CI 0.87-1.34, P = .47 and OR 1.04, 95% CI 0.84-1.28, P = .72 respectively. Target vessel revascularization, target lesion revascularization, major adverse cardiac events, and stroke were also not significantly different with OR 1.11, 95% CI 0.92-1.33, P = .28; OR 1.11, 95% CI 0.94-1.33, P = .22; OR 1.12, 95% CI 0.99-1.27; P = .07; and OR 1.13, 95% CI 0.69-1.84; P = .62 respectively. In addition, total stent thrombosis (ST) was similarly reported between BP-DES and DP-EES with OR 0.85, 95% CI 0.59-1.21; P = .37. However, even if BP-DES were associated with a higher rate of definite ST with OR 1.69, 95% CI 0.92-3.08, P = .09 and DP-EES were associated with a higher rate of probable ST with OR 0.67, 95% CI 0.38-1.17, P = .16, these results were not statistically significant.
CONCLUSIONS
Between 6 months and 3 years, BP-DES were similar in terms of cardiovascular outcomes compared to DP-EES. However, further long-term follow-up research is recommended.
Topics: Absorbable Implants; Cardiovascular Diseases; Drug Implants; Drug-Eluting Stents; Everolimus; Humans; Immunosuppressive Agents; Polymers; Randomized Controlled Trials as Topic
PubMed: 28700502
DOI: 10.1097/MD.0000000000007510 -
Drug Design, Development and Therapy 2023Fluocinolone acetonide (FAc) intravitreal implant (Iluvien) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have... (Review)
Review
Fluocinolone acetonide (FAc) intravitreal implant (Iluvien) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non-infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.
Topics: Humans; Diabetic Retinopathy; Drug Implants; Fluocinolone Acetonide; Glucocorticoids; Intravitreal Injections; Macular Edema; Retinal Diseases; Anti-Inflammatory Agents
PubMed: 37020801
DOI: 10.2147/DDDT.S403259 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2013The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and...
The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and drug release in vitro. Amixer torque rheometer (MTR) was used to characterize the rheological properties of wet mass used in pellet formulation. Mefenamic acid pellets were prepared by extrusion/spheronization techniques using microcrystalline cellulose (MCC) in combination with lactose as pellet forming agents and water as the binding liquid. Also, the prepared pellets were characterized for their particle size and in vitro drug dissolution. The results revealed that the increase in lactose weight ratio to MCC resulted in a significant reduction of both maximum torque and binder ratios, while the addition of 2 % (m/m) polyvinyl pyrolidone (PVP) to MCC-lactose influenced only the mean torque rather than the wetting liquid (water). Particle size ranged from 945 to 1089 mm and had small span values (0.56-0.67). Furthermore, an inverse relation was observed between the rheological character of pellet wet masses (expressed by peak torque) and in vitro release rate. Increasing MAloading from 2.5 to 5 and 10 % was accompanied by a decrease in dissolution rates. In conclusion, properties of MA matrix pellets could be successfully monitored by controlling the wet mass characteristics by measuring torque.
Topics: Cellulose; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Implants; Excipients; Lactose; Mefenamic Acid; Particle Size; Povidone; Rheology; Solubility; Technology, Pharmaceutical; Water
PubMed: 23482315
DOI: 10.2478/acph-2013-0009 -
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