EFFECT OF SELECTED MUCOADHESIVE POLYMERS ON PHARMACEUTICAL PROPERTIES OF CHITOSAN FORMULATIONS

The aim of this study was to develop a technical process and composition of mucoadhesive hydrogels containing benzocaine, based on different concentration ratios of the natural polymers chitosan and xanthan gum. For this purpose, lyophilisates of polymeric complexes with the quantitative ratios of 0.5:1, 1:1 and 1:0.5 chitosan to xanthan gum were prepared and subsequently used to prepare hydrogels of various concentrations. The physicochemical properties and pharmaceutical availability of benzocaine were evaluated and diffractograms and Fourier-transform infrared spectra of individual polymers and their polyelectrolyte complexes were compared. The 1:1 formulation exhibited the highest water absorption capacity and the gels showed the highest viscosity and the shortest blurring times. More chitosan increased carrier texture parameters, including hardness, cohesiveness and consistency, whereas more xanthan gum led to the longest gel blurring times and improved carrier stability. The concentration ratio of chitosan to xanthan gum in lyophilisates determined the viscosity, texture, spreadability and blurring time of the gels. Increases in lyophilisate percentage in the gels also affected the physicochemical properties of the carrier. In addition, the proportions of polymers in the mixture did not influence the availability of the drug from the prepared gel; this factor appears to depend more on the lyophilisate content in the carrier. Variations in the ratio of chitosan to xanthan gum in the polymer complex as well as lyophilisate percentage in the gel may impact the properties of the hydrogel and its efficacy as a carrier for therapeutic substances administered to the oral cavity mucosa.

Destruction of Chitosan and Its Complexes with Cobalt(II) and Copper(II) Tetrasulphophthalocyanines

Chitosan is a naturally occurring polysaccharide derived from chitin with a wide range of uses. Phthalocyanines are macroheterocyclic compounds that have a number of useful properties such as coloring and catalytic and antioxidant activity. Phthalocyanines are able to immobilize on chitosan, forming complexes with new useful properties. In this work, we evaluated the ability of phthalocyanines to increase the thermal stability of chitosan. Chitosan (CS) forms complexes with copper(II)-(CuPc) and cobalt(II)-(CoPc) tetrasulphophthalocyanines. The processes of destruction of chitosan (CS) and its complexes with sulphophthalocyanines CuPc and CoPc in oxidizing and inert atmospheres have been studied. It was established that, regardless of the atmosphere composition, the first chemical reactions taking place in the studied systems are elimination reactions. The latter ones in the case of chitosan and complex CS-CuPc lead to the formation of spatially crosslinked polymer structures, and it causes the release of CuPc from the polymer complex. It was found that in the case of CS-CoPc elimination reactions did not lead to the formation of crosslinked polymer structures but caused the destruction of the pyranose rings with a partial release of CoPc. Metallophthalocyanines showed antioxidant properties in the composition of complexes with chitosan, increasing the temperature of the beginning of glycosidic bond cleavage reaction by 30–35 °C in comparison with the similar characteristics for chitosan.

DRYING OF THE NEW WATER-SOLUBLE POLYMER COMPLEX OF ALBENDAZOL WITH PECTIN

The drying process of the aqueous solution of the complex of Albendazole with pectin (Alpec) in a vacuum oven and by spray drying was studied. It was found that the drying in a nozzle-type spray dryer is preferable in yield and subsequent solubility of the final product. As a result of the studying of the parameters affecting to the drying process, the optimal mode of the dryer was established, which provides the high yield of the dry product: the temperature of the coolant at the inlet is 130–140 °С, the output is 60–70 °С, the solution flow rate is 2.5 l/h·min. The yield of the dry product is 85%. The comparative IR spectra of Alpec powder after spray drying, after drying in air, the starting Albendazole and pectin unambiguously indicate that the structure of the complex of Albendazole with pectin (Alpec) is identical after different types of drying. The biological activity of Alpec dry substance after spray drying compared with Albendazole was studied. The increased biological activity of Alpec compared with Albendazole was established, which can, probably, be explained by the good water solubility of Alpec in contrast to Albendazole and, as a consequence, the increase of bioavailability of the drug. It was found that the average lethal dose of Alpec (LD50) is 680 (601.8–768.4) mg·kg-1 (LD50 Albendazole - 400.2–450.4 mg·kg-1), i.e. the drug "Alpec" in terms of acute toxicity during intragastric use is classified as moderately hazardous substances. On the base of the results obtained, the technology of the obtaining of the anthelmintic drug alpec substance in the form of a water-soluble dry powder has been developed.

Integrating layer by layer manufacturing for the realization of polymer complex geometries with scanning devices: re-building by digital data

The additive manufacturing technique represents a way to realize components or prototypes without the use of conventional tools.The research presented aims at proposing a methodology based on the use of three different techniques that are the poly-jet 3D using UV photo-polymerization, the FDM of polyamide materials and the FDM of PLA materials. The original data were used at the beginning with the first technique in order to detect the shape and the geometry by a 3D SCANNER. The objective was the re-building of a model shape made using a procedure in which the input file characteristics were updated starting from those got by the scanning device in order to respect the original requirements defined in the computer aided environment. It was found that the physical re-building of an object is depending the characteristics of the input file that needs to be digitally processed in order to get the desired shape and geometry. In that way also FDM using PLA and polyamide materials can be utilized to get components or prototypes from scanned digital data. The results are reported in details.

Formulation and evaluation of orally disintegrating tablet containing taste masked mirtazapine

Objective: This study aims to prepare the taste-masked granules of Mirtazapine by mass extrusion technique and formulate it into an oral dispersible tablet using different super disintegrates. Methods: Taste masked granules of mirtazapine were prepared by mass extrusion technique using Eudragit EPO in different ratios. The drug-polymer ratio was optimized based on the percent drug release in SSF and SGF. Taste masking efficacy of drug-polymer complex was determined by developing the bitterness threshold value of Mirtazapine. The selected drug-polymer complex was formulated into an oro-dispersible tablet by direct compression method. A randomized design was used to investigate individual effect of three different super disintegrates each in different concentrations. Ten formulations were developed including a controlled formulation without the addition of superdisintegrants. A comparative study was done based on various pre-compression and post-compression parameters. Results: Eudragit EPO was able to mask the bitter taste of Mirtazapine effectively in 1:2 ratio by mass extrusion method. The minimum disintegration time and wetting time was found to be 13.6±2.7 and 18.13±0.24 seconds with the formulation containing crospovidone 5% (F9). It was found that the wetting time and disintegration time followed the order SSG>CCS>CPV. The selected best formulation was subjected to an incompatibility study design. The IR spectrum showed that all the excipients were chemically compatible. Conclusion: Thus, in this study unpalatable taste of Mirtazapine was masked using Eudragit EPO polymer by mass extrusion technique, and superdisintegrants were added to prepare orally disintegrating tablets of Mirtazapine. This research work suggests a rapid, simple and cost effective method for formulating Mirtazapine ODT.

A quadruple blinded placebo controlled randomised trial to evaluate the effectiveness of an Iodine complex for patients with mild to moderate COVID-19 in Pakistan (I-COVID-PK): A structured summary of a study protocol for a randomised controlled trial

Objectives The objective of the study is to measure the efficacy of ionic-iodine polymer complex [1] for clinical and radiological improvement in coronavirus disease 2019 (COVID-19) patients. Trial design The trial will be closed label, randomized and placebo-controlled with a 1:1:1:1 allocation ratio and superiority framework. Participants All PCR confirmed COVID-19 adult patients including non-pregnant females, with mild to moderate disease, will be enrolled from Shaikh Zayed Post-Graduate Medical Complex, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Patients with any pre-existing chronic illness will be excluded from the study. Intervention and comparator In this multi-armed study ionic-iodine polymer complex with 200 mg of elemental iodine will be given using three formulations to evaluate efficacy. Patients will be receiving either encapsulated iodine complex of 200 mg (arm A), iodine complex syrup form 40 ml (arm B), iodine complex throat spray of 2 puffs (arm C) or empty capsule (arm D) as placebo; all three times a day. All the 4 arms will be receiving standard care as per version 3.0 of the clinical management guidelines for COVID-19 established by the Ministry of National Health Services of Pakistan. Main outcomes Primary outcomes will be viral clearance with radiological and clinical improvement. SARS-CoV-2 RT-PCR and HRCT chest scans will be done on the admission day and then after every fourth day for 12 days or till the symptoms are resolved. RT-PCR will only be shown as positive or negative while HRCT chest scoring will be done depending on the area and severity of lung involvement [2]. Time taken for the alleviation of symptoms will be calculated by the number of days the patient remained symptomatic. 30-day mortality will be considered as a secondary outcome. Randomisation Stratification for initial COVID-19 status (or days from initial symptoms as a proxy), age groups, gender, baseline severity of symptoms and co-morbidities will be used to ensure that the study arms remain balanced in size for the 1:1:1:1 allocation ratio. Randomization will be done using the lottery method. As patients are being admitted at different times, they will be recruited after obtaining their voluntary written informed consent following all standard protocols of the infection, control and disinfection. Blinding (masking) This is a quadruple (participants, care providers, investigators and outcomes assessors) blinded study where only the study’s Primary Investigator will have information about the arms and their interventions. Numbers to be randomised (sample size) 200 patients will be randomized into four groups with three experimental and one placebo arm. Trial Status Protocol Version Number is 2.3 and it is approved from IRB Shaikh Zayed Hospital with ID SZMC/IRB/Internal0056/2020 on July 14th, 2020. The recruitment is in progress. It was started on July 30, 2020, and the estimated end date for the trial is August 15, 2021. Trial registration Clinical Trial has been retrospectively registered on www.clinicaltrials.gov with registration ID NCT04473261 dated July 16, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.