Effect of pH on Diclofenac Release from Eudragit RS100® Microparticles. A Kinetic Study by DSC

The present work is aimed at investigating the release of Diclofenac (DCF) from Eudragit RS100T® (RS) microparticles to a biological model membrane consisting of dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV). The microparticles were prepared by the Quasi-Emulsion Solvent Diffusion method (QESD). The drug release was monitored by Differential Scanning Calorimetry (DSC) technique, following the effects exerted by DCF on the thermotropic behaviour of DMPC multilamellar vesicles at different temperatures. DCF affects the transition temperature (T_m) of phospholipid vesicles, causing a m shift towards lower values, which is modulated by the drug fraction entering into the lipid bilayer. Calorimetric measurements were performed at two different pH (4.0 and 7.4) on suspensions of blank liposomes added to weighed amounts of unloaded and DCF-loaded microspheres, as well as to the powdered free drug, after incubation at 37°C. The T_m shifts, caused by the drug released from the polymeric system or by the free drug during incubation cycles, were compared to those caused by a chosen molar fractions of the free drug dispersed directly in the membrane. This in vitro study suggests as the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres as well as by the pH value, acting on drug solubility and membrane disorder.     

A Study of the Effects of Curing and Storage Conditions on Controlled Release Diphenhydramine HCl Pellets Coated with Eudragit® NE30D

The objective of this study was to investigate the possible impacts of curing and storage conditions on dissolution of controlled release diphenhydramine HCl pellets coated with EUDRAGIT® NE30D. The accumulative percentage of dissolved active drug was used as the response in three statistical experimental design studies: 3² full factorial, Box–Behnken and 2³ designs. By only considering curing temperature and curing time, both factors were found to significantly affect the dissolution rate, but curing temperature had greater impact than curing time. When considering polymer coating level, curing temperature and curing time together, polymer coating level and curing temperature had important effects on dissolution rate, but curing time became insignificant among these three factors. The addition of the water-soluble additives hydroxypropyl methyl cellulose and mannitol made coating films less sensitive to curing, and there was little or no difference in their effect in the model studied. Lower levels of a water-insoluble additive (kaolin) had little impact on dissolution; however, when the level of water-insoluble additive increased, the coating film became more sensitive to curing, especially at the lower curing temperature of 30°C.     

Dry Powder Coating of Pellets with Micronized Eudragit® RS for Extended Drug Release

PURPOSE: To develop a novel powder coating technology for extended-release pellets based on the acrylic polymer, Eudragit RS. METHODS: A mixture of micronized Eudragit RS plus talc and a liquid feed (plasticizer plus binder solution) were sprayed separately onto propranolol hydrochloride-loaded pellets in a fluidized bed coater. The coated pellets were heat-cured under different conditions (40 degrees C to 60 degrees C, 2 h to 24 h). The coalescence (film formation) of the polymer particles was studied via the determination of the glass transition and the minimum polymer-softening temperatures (MST). The coated pellets were characterized with respect to their morphologic, release, and stability properties. RESULTS: The optimum plasticizer type and concentration and process temperatures could be identified by the determination of the MST. High concentrations of plasticizer (40% based on the polymer) and a thermal treatment were necessary to achieve complete film formation and extended drug release. Curing the pellets resulted in release profiles, which did not change during storage for 3 years. The coated pellets had a smooth, continuous surface and a dense film structure after curing. CONCLUSIONS: This novel coating technique avoids the use of organic polymer solutions or latex dispersions, has short processing times, and results in stable extended-release profiles.     

Sustained-Release Curcumin Microparticles for Effective Prophylactic Treatment of Exocrine Dysfunction of Pancreas: A Preclinical Study on Cerulein-Induced Acute Pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disorder of the pancreas with considerable mortality. The clinical therapy is hampered due to lack of any approved drug for AP. In this study, we developed curcumin (cur)-loaded poly (lactic-co-glycolic acid) cur microparticles (CuMPs) for sustained release. CuMPs were prepared by emulsion solvent evaporation method and characterized for shape, size, compatibility, and entrapment efficiency. The in vitro drug release and in vivo pharmacokinetic studies confirmed sustained release pattern of cur from CuMPs. The pharmacodynamic study was conducted in cerulein induced AP model. Prophylactic treatment was planned with single dose of CuMPs (equivalent to 7.5 mg/kg of cur) and compared with free cur given orally (100 mg/kg) and intraperitoneally (7.5 mg/kg) daily for 7 days. Interestingly, the effects of CuMPs were superior compared to the free drug administered either orally or intraperitoneally through repeated administrations. CuMPs showed significant decrease of serum amylase and lipase levels, oxidative and nitrosative stress was also significantly decreased. Moreover, CuMPs impressively decreased inflammatory cytokines. Our results may pave a way to propose similar strategy for many of promising natural products to combat several oxidative stress–mediated disorders via sustained release microparticle approaches.     

Preparation and Analgesic Activity of Eudragit RS100® Microparticles Containing Diflunisal

Two different techniques, the quasi-emulsion solvent diffusion method and spray drying that provide polar and nonpolar preparation environments, were used to prepare microspheres from Eudragit RS100® (RS) (acrylic/methacrylic copolymer) incorporating the nonsteroidal anti-inflammatory drug diflunisal. The effects of pH on the preparation medium and drug/polymer ratio on production yield and drug incorporation, as well as on the in vitro drug release at pH 1.2 and 6.8 from tabletted microparticles, were evaluated. The drug-polymer interactions and the effect of diflunisal incorporation in the polymer matrix on drug crystallinity have been evaluated by using differential scanning calorimetry, IR and ultraviolet spectroscopy, x-ray diffraction, and microscopy analysis. A preliminary biological assay confirmed that diflunisal maintains its analgesic activity after intraperitoneal administration to rats.     

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

用乳剂—溶剂挥发法制备硝苯地平的丙烯酸树脂缓释微球。微球中药物的释放速度随丙烯酸树脂ＥｕｄｒａｇｉｔＲＬ／ＲＳ比率的增加以及制备时搅拌速率的增加而增大，随内相聚合物浓度的增加及微球粒径的增加而减小，释药５０％所需时间与微球粒径呈良好线性。微球的释药速率也随药物含量的增加（从４．２％到１６．７％）而增大，并快于药物结晶的溶解速率，但药物含量达２６．６％时，微球释药速率明显下降并低于药物结晶的溶解速率。用差热分析和Ｘ射线衍射分析证明，药物含量为４．２，９．４和１６．７％的微球中药物完全是以非晶态分散的，而含药２６．６％的微球中有药物结晶存在。不同微球释药低于７０％时，释放方式均符合Ｈｉｇｕｃｈｉ时间平方根方程。     

Comparative analysis for the institutions of the adulterated 

假劣药品是我国乃至全世界所共同面临的重大社会问题,它严重影响了用药安全,破坏了社会安定和谐。现通过对中美假劣药品现状和监管制度的比较分析,包括假劣药品的界定、规制措施以及受害者的救济制度等方面的比较分析,着重指出了我国假劣药品监管制度的不足,并借鉴美国先进监管经验,就完善我国假劣药品监管制度给出了若干建议,以保障用药安全。     

A rheological study of semisolid preparations of Eudragit ®

The present work studies the rheology of semisolid preparations of acrylic polymers of Eudragit^©, specifically RS 30 D, RL 30 D and NE 30 D. The parameters of shear deformation were obtained from experimental data and those of compression deformation were determined using previously obtained linear equations relating shear and compression stresses. The results, which were statistically significant, show a linear relationship between the coefficient of regression of these equations and the apparent viscosities of the different semisolid preparations, and between the independent term and the consistency index of each, and corroborate the previously demonstrated linear relationship between shear and compression stresses. The effect of the volume of the spindle used in the viscosimeter was observed in all cases. The equations relating both types of stress, obtained from semisolid preparations of Carbomer^® 940, can be used to determine the compression stresses of other semisolid preparations in this case, Eudragit^®.     

Comparative Study of the Pharmacokinetics and Bioequivalence of Meldonium and Mildronate® Preparations

Pharmaceutical Chemistry Journal - Acomparative study of the pharmacokinetics, bioequivalence, and safety of two marketed meldonium dosage forms Meldonium Organika (meldonium, 500 mg capsules,...     

Albendazole Generics—A Comparative In Vitro Study

Purpose. We sought to determine whether disintegration and dissolution behavior differs among various albendazole generic formulations obtained from third world countries and to compare them with the innovator's product. Methods. Dissolution behavior of various albendazole formulations was studied with USP Apparatus 2 in SGF_sp and in a modified SGF_sp which contained 0.1% of the nonionic surfactant Triton^® × 100. Disintegration was tested according to the European Pharmacopoeia. Results. Dissolution experiments in SGF_sp showed a wide range in rate and extent of albendazole dissolution. The innovator product released 81 percent within two hours, a profile matched by only one other formulation. For other formulations 32 to 64% was released within two hours. Use of a modified SGF_sp, containing 0.1% Triton^® × 100 to simulate the surface tension of gastric juice, resulted in less discrimination between products. The innovator product again showed the fastest and most complete dissolution, with ninety percent released within two hours. The generic formulations released between 67 and 82%, except for one formulation which achieved only 43% release. The results in SGF_sp plus Triton^® × 100 may be more meaningful than in SGF_sp, since the surface tension of the medium is closer to the physiological value. All formulations passed the disintegration test according to the European Pharmacopoeia, with disintegration times ranging from 2.5 to 11 minutes. Conclusions. Generic albendazole products vary widely in their dissolution behavior. Differences among products were greater in SGF_sp than in SGF_sp plus Triton^® × 100. These differences were not reflected in the disintegration behavior of the products.     

Tableting Lipid-Based Formulations for Oral Drug Delivery: A Case Study with Silica Nanoparticle–Lipid–Mannitol Hybrid Microparticles

Silica–lipid–mannitol hybrid (SLMH) microparticles have been developed that were compressible into high quality tablets suitable for oral dosing and delivery of poorly soluble drugs. SLMH tablets enable high lipid-loading levels (>40%) and retain the immediate release, enhanced lipase digestion and drug solubilisation performance. Specifically, we report formulation optimisation of SLMH microparticles and tablets using coumarin 102 (log P = 4.09) as a model Biopharmaceutics Classification System class II drug. SLMH tablets were acceptable according to standard British Pharmacopoeia friability, hardness and disintegration tests; this is not the case for conventional dry emulsions. Furthermore, in vitro dissolution and pancreatic-lipase-induced lipolysis studies under simulated intestinal conditions have demonstrated enzymatic-digestion-mediated drug solubilisation. SLMH microparticles and tablets are suitable as liquid lipid containing solid dosage forms for enhancing and controlling oral absorption of poorly soluble drugs. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:684–693, 2013     

A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient?

The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDE5 inhibitors have differences in their pharmacological profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDE5 inhibitors, and its use is limited to patients with mild ED. Treatment failures with oral drugs may be due to medication, clinician and patient issues. The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options.Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited efficacy. Vacuum constriction devices may be offered mainly to elderly patients with occasional intercourse attempts, as younger patients show limited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high satisfaction rates in properly selected patients.All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisation.     

Efficacy and Safety of Dorocontin? versus Sustac? in the Treatment of Stable Angina Pectoris: A Randomized,Double-Blind Comparative Trial

Background: Development of generic drugs has numerous benefits in terms of cost-efficiency and availability. Slow-release nitroglycerin is a vasodilator drug commonly prescribed for patients with angina pectoris. Objective: The objective of this study was to compare the efficacy and safety of generic slow-release nitroglycerin (Dorocontin^®) with that of the innovator brand (Sustac^®) in patients with stable angina pectoris. Methods: In this randomized, double-blind comparative trial, 110 patients were allocated to Dorocontin^® (n=67) or Sustac^® (n=43) at a dose of 6.4 mg TID, for a total period of two months. Maximum endurable MET (metabolic equivalent of task), MPI (myocardial perfusion imaging), along with changes in the ECG and biomarkers of renal (serum creatinine, BUN) and hepatic (AST, ALT, and ALP) function, lipid profile (total cholesterol, LDL-C, HDL-C, VLDL-C, and triglycerides), electrolytes (Na⁺ and K⁺), CBC-diff (RBC, WBC, Plt, Hb, Hct, MCV, MCH, MCHC, and RDW), and FBS were assessed at the baseline and at the end of the trial. The frequency of adverse events during the course of the trial was also recorded. Results: Apart from a significantly greater reduction in maximum ST depression in the Sustac^® versus the Dorocontin^® group (p=0.03), none of the functional (MET, MPI, and ECG) and paraclinical (renal function, hepatic function, lipid profile, electrolytes, and FBS) parameters significantly differed between the study groups. The mean Hb (p=0.035), Hct (p=0.045), and MCH (p=0.032) were decreased by the end of the trial in the Sustac^®, but not in the Dorocontin^® group, whilst there was no change in other CBC-diff parameters. Reported adverse events were not serious and included headache, vertigo, gastrointestinal upset, and orthostatic hypotension. The frequency of these adverse events was comparable between the study groups. Conclusion: The findings of the present trial showed comparable efficacy and safety of the generic and innovator products of slow-release nitroglycerin in the management of stable angina pectoris.     

Vanadium compounds for the treatment of human diabetes mellitus: A scientific curiosity? A review of thirty years of research

In the second part of the 1980s, and in the 1990s, a number of investigators demonstrated –mainly in streptozotocin-induced (STZ) diabetic rats-that the vanadate and vanadyl forms of vanadium possessed a number of insulin-like effects in various cells. It was hypothesized that oral vanadium could be an alternative treatment to parenteral insulin in the therapy of diabetes mellitus. However, the long-term and/or chronic administration of vanadium compounds should also mean tissue vanadium accumulation and risks of toxicity. The purpose of this review was to revise the current-state-of-the-art on the use of vanadium in the treatment of human diabetes. It has been conducted more than three decades after the first report on the beneficial insulin-mimetic effects of oral vanadium administration in STZ-diabetic rats. Although the antidiabetic effects of vanadium in STZ-diabetic rodents are well supported, in the few studies on human patients with positive results, that are available in the literature, vanadium compounds were administered during very short periods. We conclude that vanadium administration for the treatment of human diabetes is misplaced.     

Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery

Purpose  

The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery.     

A role for retinoids in the treatment of COVID-19?

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discovery of novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARS-CoV-2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses. Retinoids are a family molecules related to vitamin A that possess robust immune-modulating properties, including the ability to increase and potentiate the actions of IFN-I. Therefore, adjuvants such as retinoids, capable of increasing IFN-I-mediated antiviral responses, should be tested in combinations of IFN-I and antiviral drugs in pre-clinical studies of SARS-CoV-2.     

Angiogenesis: the new potential target for the therapy of psoriasis?

Angiogenesis is a hallmark of chronic inflammation such as psoriasis. Unraveling the pathogenesis of psoriasis shows that several proangiogenic mediators are activated and highly expressed during psoriasis. Vascular endothelial growth factor, hypoxia- inducible factor, tumor necrosis factor, interleukin-8 and angiopoietins are considered to be the main players responsible for the strong vessel formation in psoriasis. The proangiogenic milieu in the skin seems to result from a proinflammatory immune response initiated by T helper cells. Interestingly, several small molecules as well as modern biologics used for systemic therapy of psoriasis have been shown to provide not only immune regulatory effects but also influence endothelial cell biology. Thus, direct targeting of angiogenesis may not only help to understand psoriasis pathogenesis but also to develop new strategies to treat psoriasis with therapeutics that halt the angiogenesis required for the inflammatory disease.