Release Of Active Pharmaceutical Ingredients Research Articles

Structure of polymeric nanoparticles encapsulating a drug – pamoic acid ion pair by scanning transmission electron microscopy

Drug-delivery systems based on polymeric nanoparticles are useful for improving drug bioavailability and/or delivery of the active ingredient for example directly to the cancerous tumour. The physical and chemical characterization of a functionalized nanoparticle system is required to measure drug loading and dispersion but also to understand and model the rate and extent of drug release to help predict performance. Many techniques can be used, however, difficulties related to structure determination and identifying the precise location of the drug fraction make mathematical prediction complex and in many published examples the final conclusions are based on assumptions regarding an expected structure. Cryogenic scanning transmission electron microscopy imaging in combination with electron energy loss spectroscopy techniques are used here to address this issue and provide a multi-modal approach to the characterisation of a self-assembled polymeric nanoparticle system based upon a polylactic acid - polyethylene glycol (PLA-PEG) block copolymer containing a hydrophobic ion-pair between pamoic acid and an active pharmaceutical ingredient (API). Results indicate a regular dispersion of spherical nanoparticles of 88 ± 9 nm diameter. The particles are shown to have a multi-layer structure consisting of a 25 nm radius hydrophobic core of PLA and pamoic acid-API material with additional enrichment of the pamoic acid-API material within the inner core (that can be off-centre), surrounded by a 9 nm dense PLA-PEG layer all with a low-density PEG surface coating of around 10 nm thickness. This structure suggests that release of the API can only occur by diffusion through or degradation of the dense, 9 nm thick PLA-PEG layer either of which is a process consistent with the previously reported steady release kinetics of the API and counter ion from these nanoparticle formulations. Establishing accurate measures of product structure enables a link to performance by providing appropriate physical parameters for future mathematical modelling of barriers controlling API release in these nanoparticle formulations.

Challenges in sample preparation for swellable core technology tablets: Approaches for the removal of polyethylene oxide and optimization of API recovery

Swellable Core Technology (SCT) tablets, a solid oral dosage formulation designed for the controlled release of Active Pharmaceutical Ingredient (API), are made up of two distinct layers; an active layer containing the active ingredient (10–30%wt) and up to 90%wt polyethylene oxide (PEO); and a sweller layer which contains up to 65%wt PEO. The objective of this study was to develop a process to remove PEO from analytical test solutions and optimize API recovery using physicochemical properties of the API. Quantitation of PEO was performed by liquid chromatography (LC) using an evaporative light scattering detector (ELSD). This was used to build an understanding of removal of PEO using solid-phase extraction and liquid-liquid extraction techniques. A workflow was proposed to allow efficient development of analytical methods for SCT tablets with optimized sample clean-up.

Thermodynamic Modeling of the Amorphous Solid Dispersion-Water Interfacial Layer and Its Impact on the Release Mechanism.

During the dissolution of amorphous solid dispersion (ASD) formulations, the gel layer that forms at the ASD/water interface strongly dictates the release of the active pharmaceutical ingredient (API) and, hence, the dissolution performance. Several studies have demonstrated that the switch of the gel layer from eroding to non-eroding behavior is API-specific and drug-load (DL)-dependent. This study systematically classifies the ASD release mechanisms and relates them to the phenomenon of the loss of release (LoR). The latter is thermodynamically explained and predicted via a modeled ternary phase diagram of API, polymer, and water, and is then used to describe the ASD/water interfacial layers (below and above the glass transition). To this end, the ternary phase behavior of the APIs, naproxen, and venetoclax with the polymer poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) and water was modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The glass transition was modeled using the Gordon-Taylor equation. The DL-dependent LoR was found to be caused by API crystallization or liquid-liquid phase separation (LLPS) at the ASD/water interface. If crystallization occurs, it was found that API and polymer release was impeded above a threshold DL at which the APIs crystallized directly at the ASD interface. If LLPS occurs, an API-rich phase and a polymer-rich phase are formed. Above a threshold DL, the less mobile and hydrophobic API-rich phase accumulates at the interface which prevents API release. LLPS is further influenced by the composition and glass transition temperature of the evolving phases and was investigated at 37 °C and 50 °C regarding impact of temperature of. The modeling results and LoR predictions were experimentally validated by means of dissolution experiments, microscopy, Raman spectroscopy, and size exclusion chromatography. The experimental results were found to be in very good agreement with the predicted release mechanisms deduced from the phase diagrams. Thus, this thermodynamic modeling approach represents a powerful mechanistic tool that can be applied to classify and quantitatively predict the DL-dependent LoR release mechanism of PVPVA64-based ASDs in water.

Drug loaded implantable devices to treat cardiovascular disease

ABSTRACT Introduction It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site. Areas covered In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant. Expert opinion Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.

Enhanced blend uniformity and flowability of low drug loaded fine API blends via dry coating: The effect of mixing time and excipient size

Although previous research demonstrated improved flowability, packing, fluidization, etc. of individual powders via nanoparticle dry coating, none considered its impact on very low drug loaded blends. Here, fine ibuprofen at 1, 3, and 5 wt% drug loadings (DL) was used in multi-component blends to examine the impact of the excipients size, dry coating with hydrophilic or hydrophobic silica, and mixing times on the blend uniformity, flowability and drug release rates. For uncoated active pharmaceutical ingredients (API), the blend uniformity (BU) was poor for all blends regardless of the excipient size and mixing time. In contrast, for dry coated API having low agglomerate ratio (AR), BU was dramatically improved, more so for the fine excipient blends, at lesser mixing times. For dry coated API, the fine excipient blends mixed for 30 min had enhanced flowability and lower AR; better for the lowest DL having lesser silica, likely due to mixing induced synergy of silica redistribution. For the fine excipient tablets, dry coating led to fast API release rates even with hydrophobic silica coating. Remarkably, the low AR of the dry coated API even at very low DL and amounts of silica in the blend led to the enhanced blend uniformity, flow, and API release rate.

Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension.

Transdermal delivery of active pharmaceutical ingredients (APIs) can be challenging, since the skin possesses a rate-limiting barrier, which may be overcome when APIs possess certain ideal physicochemical properties. The lack thereof would require that APIs be included in drug delivery vehicles to enhance skin permeation. Hence, diclofenac was incorporated into various drug delivery vehicles (i.e., nano-emulsions, nano-emulgels, and a colloidal suspension containing drug-loaded nanoparticles) to investigate the transdermal delivery thereof, while nano-emulsions and nano-emulgels had varying concentrations of evening primrose oil (EPO). The aim of the study was to compare the topical and transdermal diclofenac delivery from the different types of vehicles and to investigate the influence the different EPO concentrations had on diclofenac delivery. After characterization, membrane release studies were performed (to determine whether the API was successfully released from the vehicle) followed by in vitro skin diffusion studies and tape stripping (to establish whether the vehicles assisted the API in reaching the target site (transdermal delivery)). Lastly, cytotoxicity studies were conducted via methyl thiazolyl tetrazolium (MTT) and neutral red (NR) assays on human keratinocyte (HaCaT) cells. Results showed minimal cytotoxic effects at concentrations equivalent to that which had permeated through the skin, while the membrane release and in vitro skin diffusion studies indicated that the nano-emulsions and the 10% EPO vehicles increased API release and diffusion when compared to the other vehicles. However, the colloidal suspension had the highest concentrations of API within the skin. Hence, all the vehicles were non-toxic and effectively delivered diclofenac through the transdermal route.

Polymeric Excipients in the Technology of Floating Drug Delivery Systems.

The combination of targeted transport and improvement of the release profile of the active pharmaceutical ingredient (API) is a current trend in the development of oral medicinal products (MP). A well-known way to implement this concept is to obtain floating gastroretentive delivery systems that provide a long stay of the dosage form (DF) on the surface of the stomach contents. The nomenclature of excipients (Es) of a polymeric nature used in the technology of obtaining floating drug delivery systems (FDDS) is discussed. Based on the data presented in research papers, the most widely used groups of polymers, their properties, and their purpose in various technological approaches to achieving buoyancy have been determined. In addition, ways to modify the release of APIs in these systems and the Es used for this are described. The current trends in the use of polymers in the technology of floating dosage forms (FDF) and generalized conclusions about the prospects of this direction are outlined.

Controlled Release of DNA Binding Anticancer Drugs from Gold Nanoparticles with Near-Infrared Radiation

Traditional chemotherapies target rapidly developing cells in the human body resulting in harsh side effects including fatigue, immune system suppression, and nausea, among others. Delivery systems to focus the active pharmaceutical ingredients (APIs) to the diseased tissue can diminish the negative side effects while improving treatment outcomes. Gold nanoparticles (AuNP) offer many unique advantages as drug delivery vehicles, including being biologically inert, easily adaptable to various shapes and sizes, able to create a strong Au-thiol bond, and able to generate heat upon the absorption of near-infrared light. To this end, a AuNP delivery vehicle was engineered to load and release two DNA binding anti-cancer drugs, mithramycin and doxorubicin, in a controlled fashion. The drugs were loaded onto the surface of the AuNP with temperature sensitive linkages. The amount of heat generated, and subsequent release of the drugs was controlled by the irradiation time with a near-infrared laser. By modulating the linkage used to load the drugs three different release profiles were able to be achieved, indicating the feasibility of such a system for combinational therapy requiring sequential release of APIs.

Impact of Excipients and Seeding on the Solid-State Form Transformation of Indomethacin during Liquid Antisolvent Precipitation.

Long-acting injectables are a unique drug formulation strategy, providing a slow and sustained release of active pharmaceutical ingredients (APIs). In this study, a novel approach that combines liquid antisolvent precipitation with seeding to obtain a stable form of the API indomethacin while achieving the desired particle size distribution is described. It was proven that when a metastable form of indomethacin was initially nucleated, the rate of its transformation to the stable form was influenced by the presence of excipients and seeds (17.10 ± 0.20 μm), decreasing from 48 to 4 h. The final particle size (D50) of the indomethacin suspension produced without seeding was 7.33 ± 0.38 μm, and with seeding, it was 5.61 ± 0.14 μm. Additionally, it was shown that the particle size distribution of the seeds and the time point of seed addition were critical to obtain the desired solid-state form and that excipients played a crucial role during nucleation and polymorphic transformation. This alternative, energy-efficient bottom-up method for the production of drug suspensions with a reduced risk of contamination from milling equipment and fewer processing steps may prove to be comparable in terms of stability and particle size distribution to current industrially accepted top-down approaches.

Explaining the Release Mechanism of Ritonavir/PVPVA Amorphous Solid Dispersions.

In amorphous solid dispersions (ASDs), an active pharmaceutical ingredient (API) is dissolved on a molecular level in a polymeric matrix. The API is expected to be released from the ASD upon dissolution in aqueous media. However, a series of earlier works observed a drastic collapse of the API release for ASDs with high drug loads (DLs) compared to those with low DLs. This work provides a thermodynamic analysis of the release mechanism of ASDs composed of ritonavir (RIT) and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA). The observed release behavior is, for the first time, explained based on the quantitative thermodynamic phase diagram predicted by PC-SAFT. Both liquid–liquid phase separation in the dissolution medium, as well as amorphous phase separation in the ASD, could be linked back to the same thermodynamic origin, whereas they had been understood as different phenomena so far in the literature. Furthermore, it is illustrated that upon release, independent of DL, both phenomena occur simultaneously for the investigated system. It could be shown that the non-congruent release of the drug and polymer is observed when amorphous phase separation within the ASD has taken place to some degree prior to dissolution. Nanodroplet formation in the dissolution medium could be explained as the liquid–liquid phase separation, as predicted by PC-SAFT.

A New Class of Tunable Acid-Sensitive Linkers for Native Drug Release Based on the Trityl Protecting Group.

Core-cross-linked polymeric micelles (CCPMs) are a promising nanoparticle platform due to favorable properties such as their long circulation and tumor disposition exploiting the enhanced permeability and retention (EPR) effect. Sustained release of covalently linked drugs from the hydrophobic core of the CCPM can be achieved by a biodegradable linker that connects the drug and the core. This study investigates the suitability of trityl-based linkers for the design of acid-triggered native active pharmaceutical ingredient (API) release from CCPMs. Trityl linker derivatives with different substituent patterns were synthesized and conjugated to model API compounds such as DMXAA-amine, doxorubicin, and gemcitabine, and their release kinetics were studied. Hereafter, API release from CCPMs based on mPEG-b-pHPMAmLac block copolymers was investigated. Variation of the trityl substitution pattern showed tunability of the API release rate from the trityl-based linker with t1/2 varying from <1.0 to 5.0 h at pH 5.0 and t1/2 from 6.5 to >24 h at pH 7.4, all at 37 °C. A clear difference in release kinetics was found between gemcitabine and doxorubicin, with gemcitabine showing no detectable release for 72 h at pH 5.0 and doxorubicin showing a t1/2 of less than 1 h. Based on these findings, we show that the reaction mechanism of trityl deprotection plays an important role in the API release kinetics. The first step in this mechanism, which is protonation of the trityl-bound amine, is pKa-dependent, which explains the difference in release rate. In conclusion, acid-sensitive and tunable trityl linkers are highly promising for the design of linker–API conjugates and for their use in CCPMs.

Active Pharmaceutical Ingredients Transportation and Release from Aerogel Particles Processes Modeling

In this work, active pharmaceutical ingredients release from aerogel particles and active pharmaceutical ingredients transportation processes were investigated. Experimental studies were carried out on the release of various types of active pharmaceutical ingredients from various types of aerogel particles. Release curves were obtained. A hybrid model using the lattice Boltzmann method and a cellular automata approach to simulate the release of active pharmaceutical ingredients from aerogel particles and active pharmaceutical ingredients transport processes is proposed. The proposed model can be used in new drug development, which allows partially replacing full-scale experiments with computational ones, therefore reducing the experimental studies cost.

Comparative study of specific activity of the piroctone olamine semisolid dosage form for external use

The external treatment of seborrheic dermatitis of the scalp depends on the withdrawal of clinical symptoms and the complaints the patient made to the doctor. At present Ukrainian dermatology has several dozen pharmacotherapeutic products in this direction, with dominating medicines of ketoconazole, zinc pyrition, and their combinations. They are characterized by the short-term or weak effect, associated with the pathogenic microorganisms’ resistance against the background of long-term use of biologically active substances which are their active parts. One way to solve the problem is using the drugs with new highly active pharmaceutical ingredients. Employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University proposed the composition of a new applicate semisolid dosage form of pirocton olamine based on complex physical-chemical, pharmacotechnological, biopharmaceutical, and rheological investigations – topical ointment on the hydrophilic base in combination with resin-free naphthalene for external use in the complex etiotropic treatment of seborrheic dermatitis of the scalp. The aim of this work is to study the specific activity of the combined ointment with pirocton olamine and resin-free naphthalene on a hydrophilic vehicle. Materials and methods. As the object of preclinical studies used experimental ointment containing 1 % piroctone olamine and 5 % resin-free naphthalene on the base of sodium carboxymethylcellulose glycerogel, providing optimum release of active pharmaceutical ingredients from the vehicle, and appropriate placebo semisolid dosage form. The study of the specific activity of the developed ointment under the conditional name “Oktonaf” was carried out by evaluating its antimicrobial, anti-inflammatory, and antioxidant effects given the foreseeable therapeutic focus and the literature on the spectrum of biological activity of active substances. The anti-inflammatory and antioxidant action of the proposed composition was evaluated by the allergic contact dermatitis model. As a reference drug cream “Psoricap” (KMP, Ukraine), which has long been applied in dermatological practice was used. Results of comparative microbiological studies proved that composite anti-seborrheic ointment with piroctone olamine and resin-free naphthalene by the antibacterial effect in relation to the size of the growth delay zones for Staphylococcus aureus and Escherichia coli (gram-positive and gram-negative microorganisms) slightly exceeds the effective dermatological medication reference cream “Psoricap”. At the same time, the antimycotic activity of experimental ointment in relation to Candida albicans practically does not differ from the same reference drug. A study of antioxidant and anti-inflammatory activity of the developed piroctone olamine ointment on a hydrophilic basis using the model of allergic contact dermatitis revealed that its level reliably was exceed the efficacy of topical reference medication “Psoricap”. Conclusions. Obtained data of a spectrum of specific activity of a combined ointment with piroctone olamine and resin-free naphthalene can predict the high clinical value of the proposed drug for practical domestic dermatology.

Study of structural-mechanical properties for choosing the basis of pharmaceutical composition in ointment form

Rational treatment of wounds is a pressing problem of our time, especially during hostilities. Practice has shown that currently there is no universal method of local wound healing. Therefore, a differentiated approach to the development of drugs for the local treatment of the wound process is needed. Among the dosage forms for topical use, soft drugs are a convenient dosage form for topical use. Thanks to the excipients which are a part of soft medicines, it is possible to regulate release of active pharmaceutical ingredients that, in turn, provides medical action of drug. The technology of drug preparation, which includes the substantiation of the temperature regime of drug production, the study of their physico-chemical and structural-mechanical properties affects the therapeutic efficacy of the drug.&#x0D; The aim of the work was to study the structural and mechanical properties of model samples for choosing the basis of the pharmaceutical composition in the form of an ointment.&#x0D; The object of the study were model samples of bases made on the basis of oil/water emulsion and water/oil. Measurements of rheological parameters of ointment bases and their homogeneity were performed according to the methods of the State Pharmacopoeia of Ukraine (2.2.10 and SPU 1 in Annex I).&#x0D; Studies of thermal stability and colloidal stability were performed according to DSTU 4765: 2007. Cosmetic creams. General technical conditions. [Effective from 2009-01-01]. Rheological studies of model samples of ointment bases immediately after their manufacture and their physicochemical properties (homogeneity, thermal stability and colloidal stability) both after fabrication and during 6 months of storage at room temperature. It is proved that all samples have elastic-plastic-viscous properties, thixotropy and ability to lubricate well, homogeneity and thermal and colloidal stability.&#x0D; The study of the structural and mechanical properties of model bases has shown that these samples of bases can be used as carriers of drugs in the development of soft drugs.&#x0D; The prospect of this study is to study the osmotic properties of model samples in order to choose the basis that the medical and biological requirements will meet a certain phase of the wound process.

Polymer Coated Polymeric (PCP) Microneedles for Controlled Delivery of Drugs (Dermal and Intravitreal)

Microneedles are used to deliver drugs topically across the skin and mucous membranes. Dissolvable microneedles are made using soluble polymers, which disintegrates in the tissue and release the entire payload instantaneously including the polymer construct. Often, a slow release of drug into the tissue is desirable to overcome the severity of side effects at the site of administration as well as systemic adverse effects. In addition, controlled release of active pharmaceutical ingredient (API) only (not the excipients) is safe and effective particularly when the drug delivery is intended to sensitive organs like the eye. In this project, the feasibility of fabricating polymer coated polymeric (PCP) microneedles to achieve a gradual release of only the active ingredient from the device was investigated. The potential application of such PCP microneedles in the dermal and intravitreal drug delivery was also explored using animal tissue models. The PCP microneedles were found to be intact even after prolonged contact with the release medium. The time at which 50% (T50%) of dextran (10 K) was released in case of microneedles prepared using 20% of core polymer (PVP-K30) was about 15 min versus less than 5 min in the case of uncoated microneedles. Whereas when the core polymer concentration was increased to 50%, the T50% was increased to 90 min. The rate of release depended on the polymer molecular weight grade. The rate of drug release was not influenced by the total amount of concentration of dextran. The PCP microneedles of lidocaine hydrochloride could constantly release the drug for up to 9 h in the skin tissue. Likewise, the PCP microneedles infused voriconazole, intravitreally for 6 h.

Application and Multi-Stage Optimization of Daylight Polymer 3D Printing of Personalized Medicine Products

Additive technologies have undoubtedly become one of the most intensively developing manufacturing methods in recent years. Among the numerous applications, the interest in 3D printing also includes its application in pharmacy for production of small batches of personalized drugs. For this reason, we conducted multi-stage pre-formulation studies to optimize the process of manufacturing solid dosage forms by photopolymerization with visible light. Based on tests planned and executed according to the design of the experiment (DoE), we selected the optimal quantitative composition of photocurable resin made of PEG 400, PEGDA MW 575, water, and riboflavin, a non-toxic photoinitiator. In subsequent stages, we adjusted the printer set-up and process parameters. Moreover, we assessed the influence of the co-initiators ascorbic acid or triethanolamine on the resin’s polymerization process. Next, based on an optimized formulation, we printed and analyzed drug-loaded tablets containing mebeverine hydrochloride, characterized by a gradual release of active pharmaceutical ingredient (API), reaching 80% after 6 h. We proved the possibility of reusing the drug-loaded resin that was not hardened during printing and determined the linear correlation between the volume of the designed tablets and the amount of API, confirming the possibility of printing personalized modified-release tablets.

Novel Hydrogels for Topical Applications: An Updated Comprehensive Review Based on Source.

Active pharmaceutical ingredients (API) or drugs are normally not delivered as pure chemical substances (for the prevention or the treatment of any diseases). APIs are still generally administered in prepared formulations, also known as dosage forms. Topical administration is widely used to deliver therapeutic agents locally because it is convenient and cost-effective. Since earlier civilizations, several types of topical semi-solid dosage forms have been commonly used in healthcare society to treat various skin diseases. A topical drug delivery system is designed primarily to treat local diseases by applying therapeutic agents to surface level parts of the body such as the skin, eyes, nose, and vaginal cavity. Nowadays, novel semi-solids can be used safely in pediatrics, geriatrics, and pregnant women without the possibility of causing any allergy reactions. The novel hydrogels are being used in a wide range of applications. At first, numerous hydrogel research studies were carried out by simply adding various APIs in pure form or dissolved in various solvents to the prepared hydrogel base. However, numerous research articles on novel hydrogels have been published in the last five to ten years. It is expected that novel hydrogels will be capable of controlling the APIs release pattern. Novel hydrogels are made up of novel formulations such as nanoparticles, nanoemulsions, microemulsions, liposomes, self-nano emulsifying drug delivery systems, cubosomes, and so on. This review focus on some novel formulations incorporated in the hydrogel prepared with natural and synthetic polymers.

Comprehensive study for the development of rectal suppositories with diosmin and hesperidin

The aim. To conduct a comprehensive study of biphasic-type suppositories that contain diosmin and hesperidin.&#x0D; Materials and methods. Samples of biphasic-type suppositories with a mass of 4.0 were objects of the study. Pharmacological, technological and analytical research methods were used to directly or indirectly analyze the strength and completeness of the drug activity. Thus, in this work we combined the study of the specificity of the pharmacological action of the drug, experimental verification of the quantitative content of API, analysis of the structural properties of suppositories and study of the profile of the release of active pharmaceutical ingredients.&#x0D; Results. Therefore, based on the obtained data, the most effective dose was 75 mg / kg (in terms of a human dose of 300 mg per suppository). The drug in the selected dose showed a significant therapeutic effect, which significantly exceeded that of the test sample at a lower dose and the reference agent. According to the results of technological studies, it was determined that all samples of suppositories had satisfactory structural and mechanical properties. Studies of the histological structure of the mucous membrane of rats proved that there is a positive effect of treatment with suppositories with diosmin and hesperidin due to the improvement of the normal condition of the mucous membrane, the absence of edema and ulcerative defect. Research of the release profile of active pharmaceutical ingredients showed that the best percentage of release is characteristic of sample 2 (99.8 %)&#x0D; Conclusions. Therefore, suppositories with diosmin and hesperidin in therapeutically dose of 75 mg/kg of animal weight can be used for further research and will be of interest in the treatment of hemorrhoids of both acute and chronic forms

Osmotic tablet coatings: Drying stress, mechanical properties and microstructure

The coatings in osmotic tablets play a critical role in controlling the release of active pharmaceutical ingredient. Coatings are formed by spraying dilute polymer solution onto the tablet surface. During drying, the films develop shrinkage stress, which can cause cracking. The coatings are also subject to large tensile stress generated by osmotic pressure during the dissolution process, which may rupture the coating. Despite the role of tensile stress in causing fracture in osmotic tablet coatings, a rigorous quantification of the drying stress, mechanical properties and microstructure is missing. The present work fills this gap via detailed measurement of drying stress, Young’s modulus and fracture properties of osmotic tablet coatings of cellulose acetate mixed with two different plasticisers, namely polyethylene glycol and hydroxypropyl cellulose. The measurements were complemented with imaging of the surface and the cross-section of films using scanning electron microscopy so as to relate the drying stress and mechanical properties to the microstructure of the films. The phase separation during the drying process increases the pore size, while simultaneously decreasing the modulus and the peak drying stress of the drying films. The results suggest that films with strong adhesion to the tablet surface will not rupture but if the films delaminate, the drying stress are sufficiently large to cause rupture. The detailed study presented here provides guidelines to the formulator for designing rupture-free osmotic coatings.