Release Of Propranolol Research Articles

Analytical QbD for the optimization of a multimode HPLC method for the investigation of hydrochlorothiazide, diltiazem and propranolol release from 3D printed formulation

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 – 0.90 μg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs).

Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API’s). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API’s (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the “cheerios effect” that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API’s of the formulation and the resemblance of their PK behavior with previously reported data.

Rolled-up gastroretentive oral dosages for controlled release of riboflavin and propranolol

We present a simple approach to make gelatin gastroretentive oral dosages for controlled release of riboflavin and propranolol. The approach is based on rolling-up of thin self-adhesive gelatin films, on which the reservoirs of the drugs are formed by casting. The radial position of the reservoir and, hence, the lag time and the rate of the drugs release are determined by the lateral position of the reservoir on the film before rolling. Gelatin is stabilized against dissolving in the gastric environment by enzymatic cross-linking mediated by transglutaminase (Tgase). The dosages, which have the form of tight scrolls, are stabilized against unrolling by the crosslinking of the consecutive layers. The scrolls swell in the release media, Fasted State Simulated Gastric Fluid (FaSSGF), to the dimensions which make difficult their passage by the human pyloric sphincter, but remain mechanically robust to resist the stomach peristaltic contractions during at least 24 h, sufficient for the drug release. Eventually the scrolls are degraded by the release media and can be evacuated from the stomach.

3D printing of customized bioceramics for promoting bone tissue regeneration by regulating sympathetic nerve behavior.

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block β-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.

Metal-organic frameworks for efficient mephedrone detoxification or supervised withdrawal – synthesis, characterisation, and in vivo studies

In this study, we describe the innovative use of metal–organic frameworks (MOFs) as propranolol (PRO) carriers for mephedrone (4-MMC) overdose treatment or supervised withdrawal. The group of model Zr-based MOFs including UiO-66, UiO-67, MOF-808, and NU-1000, and PRO@MOF composites were synthesised and characterised. The PRO release was tested in water and simulated body fluid (SBF) environments. The prepared PRO@MOF differed in the amount and pore sizes, as well as in the surface properties, which affected the kinetics of PRO release. The inhibitory effect of SBF resulted in a more gradual, and controlled PRO release from PRO@MOF composites, further confirming the feasibility of this type of solution in real applications. The sorption mechanism in prepared PRO@MOF composites was studied by molecular dynamics (MD) and density functional theory (DFT) calculations. The molecular calculations (ring orientation, partial charges and bond orders) confirmed π–π stacking as the main contribution to the interaction between the electronic structures of PRO molecule and MOFs linker. The in vivo studies demonstrated the lack of cytotoxicity of MOFs and composites, and pre-evidence confirmed the effectiveness of using PRO-loaded MOFs as drug carriers in a 4-MMC overdose. The study provides a new potential detoxification system for addicts.

Propranolol as a Model Drug to Treat Smoking Cessation and its Formulation as a Transdermal Patch for Effective Management

Background: Smoking causes cancer, heart attacks, and stroke and leads to asthma and breathing problems. Nicotine replacement therapy (NRT) is considered one of the most widely accepted methods to quit smoking. However, it can lead to relapsed physical and psychological dependence. Aim: The present study aimed to explore propranolol, as a model drug to treat relapsed physical and psychological dependence due to NRT in smoking cessation. Furthermore, for its effective management, the transdermal drug delivery system has opted for the effective and long-term release of propranolol. Objective: The objective of the present study was to investigate and establish the molecular associations between propranolol with different targets associated with smoking cessation. Material and Methods: The molecular association of propranolol with eight different potential targets, namely, Acetylcholine Binding Protein (AChBP), Cannabinoid Receptor, CB1 and CB2, Monoamine oxidase (MAO), human dopamine D3 receptor, kainite, Leu- biogenic amine transporters (BAT) and α- type peroxisome proliferator-activated receptor, was studied via molecular simulation models. Polymeric films containing propranolol HCI were prepared and evaluated to select a suitable formulation for developing transdermal drug delivery systems (TDDS). Films containing different ratios of HPMC K4M, HPMC 15M, and Sodium CMC were prepared by the solvent evaporation technique using PEG 4000 incorporated as a plasticizer, and SLS was used to act as a penetration enhancer. Manufactured transdermal films were physically evaluated for thickness, weight uniformity %, moisture content %, moisture uptake %, drug content % and folding endurance. Results: Results indicated that propranolol can interact with all eight receptors at the active binding site. It was found to show considerable interaction with Acetylcholine Binding Protein (AChBP), MAO, human dopamine D3 receptor, kainite, and Leu- biogenic amine transporters (BAT) with the binding energy of -6.27, -6.74, -7.07, -6.84, and -6.63 kcal/mol, respectively. The release rate of propranolol HCI decreased linearly with increasing polymer concentration in the film and depended on the film thickness. In contrast, the quantity of drug release was proportional to the square root of time. Kinetic data based on the release exponent, ‘n’ in the Peppas model showed that n values were between 0.95 and 1.08, indicating that drug release from polymer matrix was predominantly by diffusion with swelling. Conclusion: Transdermal drug delivery of propranolol could act as a potential regulator of all studied targets associated with physical and psychological dependence associated with NRT and smoking cessation. Furthermore, propranolol-loaded transdermal patches with optimized release could be utilized to deliver the drug with optimum bioavailability for a considerable time.

Bioprinted Scaffold Remodels the Neuromodulatory Microenvironment for Enhancing Bone Regeneration

AbstractHerein, a 3D bioprinted scaffold is proposed, containing a calcitonin gene‐related peptide (CGRP) and the β‐adrenergic receptor blocker propranolol (PRN) as a new method to achieve effective repair of bone defects. By leveraging the neuromodulation mechanism of bone regeneration, CGRP and PRN loaded mesoporous silica nanoparticles are added into a hybrid bio‐ink, which initially contains gelatin methacrylate, Poly (ethylene glycol) diacrylate and bone marrow mesenchymal stem cells (BMSCs). Subsequently, the optimized bio‐ink is used for 3D bioprinting to create a composite scaffold with a pre‐designed micro‐nano hierarchical structure. The migration and tube formation of human umbilical vein endothelial cells (HUVECs) can be promoted by the scaffold, which is beneficial to the formation of a new capillary network during the bone repair process. With the release of CGRP from the scaffold, the secretion of neuropeptides by sensory nerves is simulated. Meanwhile, the release of PRN can inhibit the binding process of catecholamine to β‐adrenergic receptor, co‐promoting the osteogenic differentiation of BMSCs with CGRP and silicon ions, which will effectively enhance bone repair of a critical‐sized cranial defect in a rat model. In conclusion, this study provides a promising strategy for bone defect repair by understanding the neuromodulatory mechanisms during bone regeneration.

Sequential Drug Release Achieved with Dual‐Compartment Microcontainers: Toward Combination Therapy

AbstractCombination drug therapy is commonly used to treat cancer, diabetes, cardiovascular conditions, and infections. However, these therapies face challenges associated with patient compliance and toxicology. Over the past decades, microdevices have emerged as a promising candidate for oral delivery allowing for targeted drug delivery with a tunable drug release. In the present work, engineered and monodisperse dual‐compartment microdevices are developed to achieve a physical separation of two drugs followed by a sequential release in the gastrointestinal tract. As proof‐of‐concept, the compartments are sealed with two pH‐sensitive polymers of different thicknesses to control the sequential release of propranolol and furosemide. In vitro release studies and in vivo absorption studies in rats confirm a sequential drug release from the two compartments. Unlike other proposed approaches, it is highly advantageous that the drugs can be loaded directly as powders, and that their release can be tuned via optimized coatings to achieve the desired release and absorption profiles. Conclusively, this study lays a strong foundation for the future use of microdevices to enable co‐delivery of drugs followed by a sequential release in close proximity in the gastrointestinal tract.

Physicochemical Evaluation and Formulation of Propranolol Niosomal Gel with a Potential Effect on Infantile Hemangioma

Introduction: Propranolol is a non-specific beta-blocker that is used to treat hypertension, angina, arrhythmia, tremor, and manage thyrotoxicosis. Based on the results of various studies, propranolol can control infantile hemangioma by vasoconstriction, apoptosis induction, and inhibition of cell proliferation signals. Methods: The conventional film hydration method was used to prepare medium size (2-6 m) multilamellar vesicles (MLVs) containing propranolol. At the lipid phase, sorbitan esters (Spans) and their polyethoxylated derivatives (Tweens) were combined with cholesterol, and deionized water was utilized as a hydration medium. Laser light scattering was used to perform the size analysis, and the Franz diffusion cells were utilized to investigate the release of propranolol from niosomal suspensions and carbomer-based niosomal gels. The vesicles were assessed for their stability within six-month storage at 4°C, and ultraviolet spectrophotometer and centrifuge technique were employed to measure the efficiencies of encapsulation. Results: Based on the findings, the best niosomes were obtained at 40 and 60 spans in the presence of Tween 40 and 60; however, Span/Tween 20 and 80 were not able to form propranolol niosomes. The selected formulations had an MLV appearance and size distribution of 5 μm. Encapsulation efficiency and release rate of selected niosomes were optimal. Niosomes had good stability during six months of storage at refrigerator temperature. Conclusions: Based on the obtained results in this study, the application of a new topical dosage form of propranolol showed promising results for the treatment of infantile hemangioma

Anion-responsive self-assembled hydrogels of a phenylalanine-TREN conjugate allow sequential release of propranolol and doxorubicin.

Stimuli-responsive self-assembled and supramolecular hydrogels derived from peptide amphiphiles have opened exciting new avenues in biomedicine and drug delivery. Herein, we screened a series of phenylalanine-amphiphiles possessing polyamine and oxyethylene appendages for their self-assembly and anion-responsiveness and found that the tris(aminoethyl)amine (TREN) containing amphiphile NapF-TREN formed injectable hydrogels that could be disrupted upon the addition of stoichiometric amounts of tetrahedral monovalent anions such as H2PO4- and HSO4-, while the addition of other anions such as Cl-, HPO42-, CO32-, HCO3- or SO42- did not affect the gel stability. The anion-gelator interaction was investigated by 1H and 31P NMR spectroscopy as well as by Isothermal Titration Calorimetry (ITC). These studies confirmed a 1 : 1 stoichiometry and revealed negative enthalpy and negative entropy for the binding of H2PO4- with NapF-TREN. Microscopic investigations by TEM, AFM, and SAXS revealed that H2PO4- anions induced a nanofiber-to-nanoglobule morphological change in the aqueous self-assemblies of NapF-TREN. However, upon ageing the samples, slow reformation of the nanofibers was also observed, reflecting the reversibility of the anion-gelator interaction. The anion- and pH-responsive nature of the NapF-TREN hydrogels was exploited to program sequential release of entrapped drugs propranolol and doxorubicin.

Development, characterization, and in vitro evaluation of adhesive fibrous mat for mucosal propranolol delivery

Abstract This research focuses on the synthesis and adhesive properties of mucoadhesive mats, prepared with poly(vinylic alcohol) as a base polymer for the oromucosal release of propranolol (PRO) by the electrospinning technique. The nanofibers mats were evaluated by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry; in vitro drug entrapment efficiency, degradation time, and adhesion studies were performed. SEM images of the electrospun mats show the correct formation of fibers with a variable diameter and porosity. Thermal studies indicate excellent thermal stability of the scaffolds, The fibrous mats loaded with 10% of the drug exhibit the best thermal stability with decomposition after 450°C. In vitro studies indicate a drug content of 88% loaded in the mats. In the cytotoxicity test, loaded mat presents cell proliferations of 97% and 88% for drug concentrations of 10% an 15%, respectively. To conclude, the formed electrospun adhesive mats exhibited excellent thermal stability, adhesive properties, and drug entrapment efficiency, promising features for a successful drug topical release system on mucosal tissue in the oral cavity.

Propranolol-loaded electrospun nanofibrous wound dressing: From fabrication and characterization to preliminary wound healing evaluation.

Objective(s):The wound healing potential of beta-blocker drugs such as propranolol (PNL) has recently attracted attention. To date, incorporation of PNL into electrospun nanofibrous wound dressing mats has not been tested as a novel topical drug delivery system. Presently, electrospun nanofibrous mats loaded with PNL were fabricated, and their physicochemical properties and wound healing activities were evaluated.Materials and Methods:Polyvinyl alcohol solutions containing 0, 2% or 4% (wt/vol) PNL were electrospun into mats, and the physicochemical properties and PNL release were evaluated. In vitro biocompatibility of selected PNL-loaded mats was tested in human foreskin fibroblasts and wound healing capability was evaluated in mouse skin wounds.Results:The 4% PNL mat had thin fibers (160 nm), convincing porosity (79.5%), and good hydrophilicity (swelling: 89.1%, water contact angle: 42.1°) with little degradability (14.2%). The release of PNL was not in bursts and was best explained by the Korsmeyer–Peppas equation (R2 = 0.96, n = 0.40), suggesting Fickian release. The viability of fibroblasts was 173% on day 5 of incubation with 4% PNL mats, indicating good mat biocompatibility. In vivo treatment for 14 days with 4% PNL mats resulted in wounds with a surface area of only 9% of the original wound area. These wounds had better histopathologic characteristics and were associated with less oxidative stress.Conclusion:The wound dressing fabricated with 4% PNL showed good potential for wound healing because of a favorable drug release profile from the nanofiber scaffold, and can be considered eligible for further clinical research.

Formulation and Evaluation of Tablets Compressed from Granules Prepared by Thermoplastic Granulation

Abstract The aim of this formulation study was to determine the effect of the binder used in the preparation of granules by thermoplastic granulation on the release of propranolol from experimental tablets. Another aim was to select suitable excipients and their ratio in the granules to ensure a trouble-free formulation of the tablets. This study proved that the binder affects the flow properties of the granules, disintegration of the tablets and, subsequently, also the method of drug release, which can be used for the preparation of tablets with modified or prolonged drug release.

Blockade of adrenergic β-receptor activation through local delivery of propranolol from a 3D collagen/polyvinyl alcohol/hydroxyapatite scaffold promotes bone repair in vivo.

ObjectivesActivation of the sympathetic system and adrenergic β‐receptors following traumatic bone defects negatively impairs bone regeneration. Whether preventing β‐receptor activation could potentially improve bone defect repair is unknown. In this study, we investigated the effect of systematic administration and local delivery of propranolol through composite scaffolds on bone healing.Materials and methodsCollagen/PVA/propranolol/hydroxyapatite（CPPH）composite scaffolds were fabricated with 3D printing technique and characterized by scanning electron microscope (SEM). Micro‐CT analysis and bone formation histology were performed to detect new bone formation. Osteogenic differentiation of bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow monocytes cultured with scaffolds extract were performed for further verification.ResultsIntraperitoneal injection of propranolol did not significantly improve bone repair, as indicated by micro‐CT analysis and bone formation histology. However, CPPH scaffolds exhibited sustained release of propranolol in vitro and significantly enhanced bone regeneration compared with vehicle collagen/PVA/hydroxyapatite (CPH) scaffolds in vivo. Moreover, in vitro experiments indicated the scaffolds containing propranolol promoted the osteogenic differentiation and migration of rat BMSCs and inhibited osteoclastogenesis by preventing β‐receptor activation.ConclusionsThis study demonstrates that local adrenergic β‐receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.

SAT-589 Thyrotoxic Periodic Paralysis: A Rare Presentation of Thyrotoxicosis

Background. Periodic paralysis (PP) is a rare muscle disorder caused by ion channel dysfunction and manifesting as episodes of painless muscle weakness. Most cases of PP are autosomal dominant, though thyrotoxic PP may complicate any etiology of hyperthyroidism. We present a case of thyrotoxic PP occurring in a patient with Graves’ thyrotoxicosis. Case. A 34 year-old Caucasian male was brought to the emergency department due to abrupt onset of diffuse muscle weakness and inability to ambulate. One week prior to onset of muscle symptoms, the patient had been diagnosed with Graves’ thyrotoxicosis during evaluation of atrial fibrillation. Examination was notable for tachycardia, irregularly irregular rhythm, small and smooth goiter, 3/5 upper extremity strength, and 2/5 lower extremity strength. Admission laboratories revealed TSH < 0.03 mIU/L (0.45-5.33), free T4 2.4 ng/dL (0.5-1.3), total T3 223 ng/dL (87-178), and potassium level 2.3 mM (3.5-5.1). A regimen of high dose oral propranolol (3 mg/kg/d), methimazole (80 mg/d), supersaturated potassium iodide (SSKI), and prednisone was immediately started, and the critical care team administered 80 mEq of potassium in two divided doses during the first hospital day. By the next day, muscle weakness had resolved, and potassium level was 4.2 mM. The patient required three additional days of treatment to bring atrial fibrillation under rate control. At hospital discharge, SSKI and prednisone were stopped, and the patient was discharged home on extended release propranolol and methimazole. Unfortunately, he was lost to outpatient endocrinology follow up. Conclusion. Thyrotoxic PP occurs most commonly in association with Graves’ disease, has a very strong male predominance, usually manifests initially in the third decade of life, and is reported much more commonly in Asian populations than among other ethnic groups. In some series, thyrotoxic PP has a prevalence of approximately 10% among Asian men with Graves’ thyrotoxicosis. The prevalence of thyrotoxic PP is 0.1-0.2% in non-Asian populations. Hypokalemia of thyrotoxic PP appears to be due to increased skeletal muscle sodium-potassium ATPase activity induced by enhanced beta-adrenergic responsiveness of the ion channel and hyperinsulinemia that occur in the setting of significant thyroid hormone excess. Weakness is typically most severe in proximal muscles and lower extremities. Potassium supplementation and non-selective beta-blockade (e.g. propranolol) can rapidly reverse hypokalemia and muscle weakness, though doses of supplemental potassium exceeding 90 mEq in 24 hr predispose to rebound hyperkalemia. Restoration of euthyroidism is required to entirely eliminate episodes of thyroxic PP.

The sustained and targeted treatment of hemangiomas by propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres

We previously developed propranolol-encapsulated liposomes-in-microspheres (PLIM) to realize the sustained propranolol release for the treatment of hemangiomas. However, the liposomes released from the microspheres still lacked specificity for CD133-positive hemangioma-derived stem cells (HemSCs) which are considered to be the seeds of hemangiomas. Therefore, we hereby encapsulated propranolol-loaded CD133 aptamers conjugated liposomes in poly(lactic-co-glycolic acid (PLGA) microspheres to develop propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM), to realize the aim of the sustained and targeted therapy of hemangiomas. The evaluation of the release of propranolol from PCLIM was carried out, and the cytotoxic effect and angiogenic growth factor expression inhibitory ability of PCLIM were performed in HemSCs. The in vivo hemangioma inhibitory ability of PCLIM was also investigated in nude mice with subcutaneous human hemangiomas. PCLIM possessed a desired size of 29.2 μm, drug encapsulation efficiency (25.3%), and a prolonged drug release for 40 days. Importantly, PCLIM could inhibit HemSCs proliferation and the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF) in HemSCs to a greater extent compared with PLIM. In nude mice bearing hemangioma xenograft, PCLIM showed the best therapeutic efficacy towards hemangiomas, as reflected by remarkably decreased hemangioma volume, weight and microvessel density (MVD). Thus, our results demonstrated that PCLIM realized the sustained and targeted treatment of hemangiomas, resulting in remarkable inhibition of hemangiomas.

The role of carboxyl group of pressure sensitive adhesive in controlled release of propranolol in transdermal patch: Quantitative determination of ionic interaction and molecular mechanism characterization

Acrylic pressure sensitive adhesives (PSAs) are widely used in transdermal drug delivery system (TDDS). However, there was little research about the quantitative relationship between drug release and drug-PSAs interaction. In this study, five acrylic PSAs with different molar fraction of carboxyl group were designed and synthesized. Propranolol (PRO) was used as model drug to evaluate release profiles in the PSAs in vitro and in vivo. The drug release percent in the PSAs were 81.66, 78.22, 51.66, 21.81 and 11.73%, and their release behaviors were decreased with carboxyl group content of PSAs. Furthermore, it was found that quantity of carboxyl group of PSAs was equal to residual drug by the quantitative determination. In addition, the ionic interaction between PRO and PSAs was confirmed by FT-IR and MDSC results qualitatively. Using the FT-IR, MDSC, Flory-Huggins interaction parameters and molecular dynamic simulation, interaction strength between drug and PSAs was determined quantitatively, which demonstrated that the drug release amount decreased linearly with interaction strength. Based on above results, we proposed that the PRO was possibly binding to the carboxyl group of PSAs one-by-one, which provided references for the accurate design of TDDS.

Development of (acrylic acid/ polyethylene glycol)-zinc oxide mucoadhesive nanocomposites for buccal administration of propranolol HCl

A series of mucoadhesive nanocomposites with self disinfection properties composed of acrylic acid, polyethylene glycol and ZnO nanoparticles (AAc/PEG)-ZnO were developed for localized buccal Propranolol HCl delivery. γ-irradiation as a clean tool for graft copolymerization process was used for the preparation of (AAc/PEG) hydrogels. In suite precipitation technique was used for ZnO nanoparticles immobilization within (AAc/PEG) hydrogels. The developed (AAc/PEG)-ZnO nanocomposites were characterized by X-ray diffraction (XRD), UV–Vis spectrophotometer, energy dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM) to confirm the success of ZnO nanoparticles formation within the (AAc/PEG) matrices. The presence of ZnO nanoparticles improves the thermal stability as indicated using thermogravimetric analysis (TGA). The mucoadhesion characteristics such as hydration degree, surface pH, and mucoadhesive strength were evaluated in artificial saliva solution. The self disinfection property of the developed (AAc/PEG)-ZnO nanocomposites was investigated by examining their resistance to pathogenic microorganisms such as Staphylococcus aureus, Bacillus subtilis, and Escherichia coli using disc diffusion method. The release of Propranolol -HCl drug in artificial saliva was found to obey a non-Fickian diffusion mechanism. The obtained results suggests that (AAc/PEG)-ZnO nanocomposites could be used as mucoadhesive carrier for buccal drug delivery with efficient antibacterial properties.

A Comparative Study of Propranolol Release by In Vitro Dissolution Profiles in Pharmaceutical Formulations

A Comparative Study of Propranolol Release by In Vitro Dissolution Profiles in Pharmaceutical Formulations