Delivery Of Active Pharmaceutical Ingredients Research Articles

Microencapsulation for Pharmaceutical Applications: A Review.

In order to improve bioavailability, stability, control release, and target delivery of active pharmaceutical ingredients (APIs), as well as to mask their bitter taste, to increase their efficacy, and to minimize their side effects, a variety of microencapsulation (including nanoencapsulation, particle size <100 nm) technologies have been widely used in the pharmaceutical industry. Commonly used microencapsulation technologies are emulsion, coacervation, extrusion, spray drying, freeze-drying, molecular inclusion, microbubbles and microsponge, fluidized bed coating, supercritical fluid encapsulation, electro spinning/spray, and polymerization. In this review, APIs are categorized by their molecular complexity: small APIs (compounds with low molecular weight, like Aspirin, Ibuprofen, and Cannabidiol), medium APIs (compounds with medium molecular weight like insulin, peptides, and nucleic acids), and living microorganisms (such as probiotics, bacteria, and bacteriophages). This article provides an overview of these microencapsulation technologies including their processes, matrix, and their recent applications in microencapsulation of APIs. Furthermore, the advantages and disadvantages of these common microencapsulation technologies in terms of improving the efficacy of APIs for pharmaceutical treatments are comprehensively analyzed. The objective is to summarize the most recent progresses on microencapsulation of APIs for enhancing their bioavailability, control release, target delivery, masking their bitter taste and stability, and thus increasing their efficacy and minimizing their side effects. At the end, future perspectives on microencapsulation for pharmaceutical applications are highlighted.

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood–brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective. Novel nanomaterials are being developed to deliver APIs into the CNS to modulate glial responses and improve outcomes in injury and disease. Nanomaterials are attractive options as therapies for central nervous system protection and repair in degenerative disorders and traumatic injury due to their intrinsic capabilities in API delivery. Nanomaterials can improve API accumulation in the CNS by increasing permeation through the BBB of systemically delivered APIs, extending the timeline of API release, and interacting biophysically with CNS cell populations due to their mechanical properties and nanoscale architectures. In this review, we present the recent advances in the fields of both locally implanted nanomaterials and systemically administered nanoparticles developed for the delivery of APIs to the CNS that modulate glial activity as a strategy to improve outcomes in traumatic injury and disease. We identify current research gaps and discuss potential developments in the field that will continue to translate the use of glia-targeting nanomaterials to the clinic.

The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal/Transdermal Delivery.

The delivery of active molecules via the skin seems to be an efficient technology, given the various disadvantages of oral drug administration. Skin, which is the largest human organ of the body, has the important role of acting as a barrier for pathogens and other molecules including drugs; in fact, it serves as a primary defense system blocking any particle from entering the body. Therefore, to overcome the skin barriers and poor skin permeability, researchers implement novel carriers which can effectively carry out transdermal delivery of the molecules. Another significant issue which medical society tries to solve is the effective dermal delivery of molecules especially for topical wound delivery. The application of nanogels is only one of the available approaches offering promising results for both dermal and transdermal administration routes. Nanogels are polymer-based networks in nanoscale dimensions which have been explored as potent carriers of poorly soluble drugs, genes and vaccines. The nanogels present unique physicochemical properties, i.e., high surface area, biocompatibility, etc., and, importantly, can improve solubility. In this review, authors aimed to summarize the available applications of nanogels as possible vehicles for dermal and transdermal delivery of active pharmaceutical ingredients and discuss their future in the pharmaceutical manufacturing field.

Design and Development of Low- and Medium-Viscosity Alginate Beads Loaded with Pluronic® F-127 Nanomicelles.

The anionic polymer sodium alginate, a linear copolymer of guluronic and mannuronic acids, is primarily present in brown algae. Copolymers are used in the sodium alginate preparation process to confer on the material strength and flexibility. Micelles and other polymeric nanoparticles are frequently made using the triblock copolymer Pluronic® F-127. The purpose of the present study is to determine the effect of sodium alginate's viscosity (low and medium) and the presence of Pluronic® F-127 micelles on the swelling behavior of the prepared pure beads and those loaded with Pluronic® F-127 micelles. The Pluronic® F-127 nanomicelles have a size of 120 nm. The swelling studies were carried out at pH = 1.2 (simulated gastric fluid-SGF) for two hours and at pH = 6.8 (simulated intestinal fluid-SIF) for four more hours. The swelling of both low- and medium-viscosity alginate beads was minor at pH = 1.2, irrespective of the use of Pluronic® F-127 nanomicelles. At pH = 6.8, without Pluronic® F-127, the beads showed an enhanced swelling ratio for the first four hours, which was even higher in the medium-viscosity alginate beads. With the addition of Pluronic® F-127, the beads were dissolved in the first and second hour, in the case of the low- and medium-alginate's viscosity, respectively. In other words, the behavior of the mixed hydrogels was the same during the swelling experiments. Therefore, the presence of Pluronic® F-127 nanomicelles and medium-viscosity sodium alginate leads to a higher swelling ratio. A model drug, acetyl salicylic acid (ASA), was also encapsulated in the mixed beads and ASA's release studies were performed. In conclusion, the prepared systems, which are well characterized, show potential as delivery platforms for the oral delivery of active pharmaceutical ingredients and biopharmaceuticals.

Review of the pharmacokinetics of nanodrugs

Abstract Nanodrug delivery systems (NDDSs) are a hotspot of new drug delivery systems with great development potential. They provide new approaches to fighting against diseases. NDDSs are specially designed to serve as carriers for the delivery of active pharmaceutical ingredients to their target sites, and their unique physicochemical characteristics allow for prolonged circulation time, improved targeting, and avoidance of drug resistance. Despite remarkable progress achieved in the preparation and efficacy evaluation of NDDSs, the understanding of the in vivo pharmacokinetics of NDDSs is still insufficient. Analysis of NDDSs is far more complicated than that for small molecular drugs; thus, almost all conventional techniques are inadequate for accurate profiling of their pharmacokinetic behaviour in vivo. In this article, we systematically reviewed the absorption, distribution, metabolism, and excretion of NDDSs and summarized the advanced bioanalytic techniques for tracing the in vivo fate of NDDSs. We also reviewed the physiologically based pharmacokinetic model of NDDS, which has been a useful tool in characterizing and predicting the systemic disposition, target exposure, and efficacy/toxicity of various types of drugs when coupled with pharmacodynamic modelling. We hope that this review will be helpful in improving the understanding of NDDS pharmacokinetics and facilitating the development of NDDSs.

Preparation, Characterization and Evaluation of Flavonolignan Silymarin Effervescent Floating Matrix Tablets for Enhanced Oral Bioavailability.

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug-polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (<2 min). The formulation showed good matrix integrity and retarded the release of drug for >12 h. The dissolution can be described by zero-order kinetics (r2 = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time.

Nanotherapeutics for pulmonary drug delivery: An emerging approach to overcome respiratory diseases

Pulmonary diseases pose an immense threat to global health. Several nanotherapeutics-based approaches aimed to tackle pulmonary ailments in recent years. The current innovation includes developing nanomedicine for pulmonary delivery of active pharmaceutical ingredients, repurposed drugs, host-directed therapies, or molecules with unconventional mechanisms (such as antimicrobial peptides). But pulmonary delivery of nanomedicines is troublesome due to poor aerodynamic properties for lung deposition and expulsion during inhalation. Nanomedicine can deliver drugs directly into lung tissue via aerosol or dry powder for inhalation to target deep lung deposition and subsequent therapeutic efficacy. Particulate-based drug delivery systems are potentially complementary to conventional inhaled drugs. There are several ways to produce an aerosol or DPI-based therapeutics, and we reviewed some standard methods used to develop nanotherapeutics for inhalation. The developed inhalable formulations can be delivered using inhalation devices, and advanced inhaler device technology has allowed the efficacious delivery of therapeutic compounds via inhalation. In addition, particle engineering is a crucial criterion in developing inhalable formulations to improve drug delivery, enhance therapeutic effects, and perform superior targeting. Technological advancements in inhalation devices have improved the efficiency of lung-based drug delivery mechanisms. This review also enumerated the assessment of pulmonary drug delivery systems, i.e., in vitro, ex vivo, in vivo, or in silico models, which have made significant strides in recent years.

Liver Targeting Novel Trends In Therapies

Background: In this review Novel strategies for site-specific delivery of active pharmaceutical ingredients to different types of liver cells like Hepatic stellate cells [HSCs], active Kupffer cells, sinusoidal endothelial cells etc. have been discussed. The most prevalent liver ailments are hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic venous-occlusive disease, liver fibrosis, and cirrhosis. Method: Literature was searched through various online resources for the recent advances in liver-targeted site-specific delivery using various approaches. We focused on the use of novel targeted delivery to improve Drug efficacy, dose reduction and Rapid onset of action. Results: Novel medicines aim to minimize unfavorable side effects by either sustaining drug action at a set rate or delivering the drug at a suitable time in the body. Therapeutic nanocarriers and their surface modification with particular ligands including carbohydrates, peptides, proteins, and antibodies are two main strategies that have been suggested to optimize the transport of various medications to the liver and hepatocytes. It subsequently lowers the toxicity and prolongs the drug's time in the systemic circulation. Conclusion: The current review provides information on various liver illnesses as well as the targeting techniques used to concern hepatic anatomy and disease etiologies.

Nanomedicine strategies to improve therapeutic agents for the prevention and treatment of preterm birth and future directions.

The World Health Organisation (WHO) estimates 15 million babies worldwide are born preterm each year, with 1 million infant mortalities and long-term morbidity in survivors. Whilst the past 40 years have provided some understanding in the causes of preterm birth, along with development of a range of therapeutic options, notably prophylactic use of progesterone or uterine contraction suppressants (tocolytics), the number of preterm births continues to rise. Existing therapeutics used to control uterine contractions are restricted in their clinical use due to pharmacological drawbacks such as poor potency, transfer of drugs to the fetus across the placenta and maternal side effects from activity in other maternal systems. This review focuses on addressing the urgent need for the development of alternative therapeutic systems with improved efficacy and safety for the treatment of preterm birth. We discuss the application of nanomedicine as a viable opportunity to engineer pre-existing tocolytic agents and progestogens into nanoformulations, to improve their efficacy and address current drawbacks to their use. We review different nanomedicines including liposomes, lipid-based carriers, polymers and nanosuspensions highlighting where possible, where these technologies have already been exploited e.g. liposomes, and their significance in improving the properties of pre-existing therapeutic agents within the field of obstetrics. We also highlight where active pharmaceutical agents (APIs) with tocolytic properties have been used for other clinical indications and how these could inform the design of future therapeutics or be repurposed to diversify their application such as for use in preterm birth. Finally we outline and discuss the future challenges.

Nosači lekovitih supstanci skloni samoorganizovanju - trenutni izazovi u karakterizaciji i izgledi za budućnost

A review of recent publications reveals an increased interest in the so-called self-assembled carriers and their applicability in drug delivery via various routes of administration. Self-assembly denotes the process of rather spontaneous formation of ordered aggregates (sometimes under specific conditions-e.g., pH, temperature, ionic strength), via diverse interactions. This process, seen in many naturally occurring substances (polysaccharides, proteins, lipids), has inspired researchers to synthetize innovative self-assembling materials or combinations of existing ones. This paper provides a review of the recently investigated self-assembling materials and the carriers they form, often belonging to the sphere of pharmaceutical nanotechnology. Self-assembled carriers may provide enhanced stability, more efficient encapsulation and/or controlled delivery of active pharmaceutical ingredients. However, the diversity of geometries obtained (spheres, polyhedrals, ellipses, discs, porous structures, etc.) presents a significant characterization challenge, often requiring the application of several complementary techniques for proper evaluation of carrier size and morphology. Commonly utilized characterization techniques for investigating physico-chemical and certain biopharmaceutical properties are discussed, along with their advantages and disadvantages. Finally, the authors offer their critical opinion on the outlook of self-assembled drug carriers.

Development of cottonseed-based emulsions for encapsulation of vitamin A

Nanoemulsions are nanoscale self-assembled entities which are manufactured for improving the delivery of active pharmaceutical ingredients. Nanoemulsion technology is one of the best ways to encapsulate the functional components as it enhances the stability and bioavailability of the compound. In the present study, nanoemulsions were prepared by ultrasonic homogenization of dispersed phase (10-22%) and surfactants (3-9%) with vitamin A (0.25-2.5%). Nanoemulsions were characterized through various optical techniques and stability was assessed using thermal shock and freeze-thaw cycle. The results revealed that nanoemulsions with high percentage of surfactants were more stable and retained smaller particle size as compared to nanoemulsions with low surfactants percentage and high dispersed phase, contributed to phase separation and colour change. These emulsions can be further tested for any toxic/allergic effect on the biological model and may be incorporated into food products.

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.

Stimuli‐accelerated polymeric drug delivery systems

AbstractThe controlled delivery of active pharmaceutical ingredients to the site of disease represents a major challenge in drug therapy. Particularly when drugs have to be transported across biological barriers, suitable drug delivery systems are of importance. In recent years responsive delivery systems have been developed which enable a controlled drug release depending on internal or external stimuli such as changes in pH, redox environment or light and temperature. In some studies delivery systems with reactivity against two different stimuli were established either to enhance the response by synergies of the stimuli or to broaden the window of possible trigger events. In the present review numerous exciting developments of pH‐, light‐ and redox‐cleavable polymers suitable for the preparation of smart delivery systems are described. The review discusses the different stimuli that can be used for a controlled drug release of polymer‐based delivery systems. It puts a focus on the different polymers described for the preparation of stimuli‐sensitive systems, their preparation techniques as well as their stimuli‐responsive degradation. © 2022 The Authors. Polymer International published by John Wiley &amp; Sons Ltd on behalf of Society of Industrial Chemistry.

Advancements in Rectal Drug Delivery Systems: Clinical Trials, and Patents Perspective

The rectal route is an effective route for the local and systemic delivery of active pharmaceutical ingredients. The environment of the rectum is relatively constant with low enzymatic activity and is favorable for drugs having poor oral absorption, extensive first-pass metabolism, gastric irritation, stability issues in the gastric environment, localized activity, and for drugs that cannot be administered by other routes. The present review addresses the rectal physiology, rectal diseases, and pharmaceutical factors influencing rectal delivery of drugs and discusses different rectal drug delivery systems including suppositories, suspensions, microspheres, nanoparticles, liposomes, tablets, and hydrogels. Clinical trials on various rectal drug delivery systems are presented in tabular form. Applications of different novel drug delivery carriers viz. nanoparticles, liposomes, solid lipid nanoparticles, microspheres, transferosomes, nano-niosomes, and nanomicelles have been discussed and demonstrated for their potential use in rectal administration. Various opportunities and challenges for rectal delivery including recent advancements and patented formulations for rectal drug delivery have also been included.

Liposomal Nanoformulation as a Carrier for Curcumin and pEGCG-Study on Stability and Anticancer Potential.

Nanoformulations are regarded as a promising tool to enable the efficient delivery of active pharmaceutical ingredients to the target site. One of the best-known and most studied nanoformulations are liposomes—spherical phospholipid bilayered nanocarriers resembling cell membranes. In order to assess the possible effect of a mixture of polyphenols on both the stability of the formulation and its biological activity, two compounds were embedded in the liposomes—(i) curcumin (CUR), (ii) a peracetylated derivative of (−)-epigallocatechin 3-O-gallate (pEGCG), and (iii) a combination of the aforementioned. The stability of the formulations was assessed in two different temperature ranges (4–8 and 20 °C) by monitoring both the particle size and their concentration. It was found that after 28 days of the experiment, the liposomes remained largely unchanged in terms of the particle size distribution, with the greatest change from 130 to 146 nm. The potential decomposition of the carried substances was evaluated using HPLC. The combined CUR and pEGCG was sensitive to temperature conditions; however its stability was greatly increased when compared to the solutions of the individual compounds alone—up to 9.67% of the initial concentration of pEGCG in liposomes after 28 days storage compared to complete decomposition within hours for the non-encapsulated sample. The potential of the prepared formulations was assessed in vitro on prostate (LNCaP) and bladder cancer (5637) cell lines, as well as on a non-cancerous human lung fibroblast cell line (MRC-5), with the highest activity of IC50 equal 15.33 ± 2.03 µM for the mixture of compounds towards the 5637 cell line.

Physicochemical and stability profile of castor oil emulsions stabilized using natural and synthetic emulsifiers

Background: The quality and stability of castor oil emulsions may be influenced by the type and amount of its constituent emulsifiers. To our knowledge, the emulsifying potential of single, double, and triple-emulsifier systems comprising of Tween 20, acacia gum and methyl cellulose have never been compared. The aim of the work was to formulate castor oil emulsions stabilized using natural and/or synthetic emulsifying agents and evaluate their organoleptic, physicochemical, and stability profiles. Methods: Six types of emulsions were prepared using the spontaneous emulsification method, and characterised in terms of their physical properties; centrifugation analysis, and real-time stability profile at 25 ℃ and 40 ℃ for 90 days. Results: FT-IR analysis suggested that castor oil was compatible with all the studied emulsifiers. Tween 20-stabilised formulation (F2) and acacia gum/methyl cellulose-based samples (F5) exhibited unacceptable organoleptic attributes and/or physical properties. The physical properties of the remaining castor oil macroemulsions were satisfactory: pH (6.2 to 7.0); electrical conductivity (2253-4557 µS/cm); spreadability (0.7-2.1 cm); oil globule size (2.73-3.74 µm), and creaming index (9-18 %). The emulsions exhibited varying degree of instability over time and with elevated temperatures. The most promising emulsion was acacia gum/methyl cellulose/tween 20-stabilised sample F7: pH: 6.9, electrical conductivity: 4557 µS/cm, spreadability: 1.37 cm, oil globule size: 3.74 µm, creaming index: 9 %, and satisfactory stability profile at 25 °C and 40 °C. Conclusion: Sample F7 may serve as cream base for dermal and transdermal delivery of active pharmaceutical ingredients intended to treat various local skin problems and systemic diseases.

Transformation of nanoparticles into compacts: A study on PLGA and celecoxib nanoparticles

Oral delivery of nanoparticles possesses many advantages for delivery of active pharmaceutical ingredients (APIs) to the gastrointestinal tract. However, the poor physical stability of nanoparticles in liquid state is often a challenge. Removing water from the nanosuspensions and transforming the nanoparticles into solid particulate matter in the form of, e.g., tablets could be a potential approach to increase the stability of nanoparticles. The aim of this study was to transform nanoparticles into compacts and to investigate the redispersion of nanoparticles from compacts as well as the dissolution behavior of these compacts. DL-lactide-co-glycolide copolymer (PLGA) nanoparticles and celecoxib (CLX) nanoparticles were used as two model nanoparticle systems and fabricated into nano-embedded microparticles (NEMs) and subsequently compressed into compacts. The compacts were evaluated with respect to the redispersibility of the nanoparticles, as well as the dissolution characteristics of CLX. The results showed that the NEMs could be readily compressed into compacts with sufficient mechanical strength. The size of the redispersed PLGA nanoparticles from the compacts using 2-hydroxypropyl-β-cyclodextrin (HPβCD) as stabilizer was comparable to the original nanoparticles. In contrast, the redispersibility of CLX nanoparticles from the compacts was not as effective as for the PLGA nanoparticles evidenced by a significant increase in the size and polydispersity index (PDI) of the redispersed nanoparticles. Nonetheless, an obvious enhancement in dissolution rate of CLX was observed from the compacts with CLX nanoparticles. It is concluded that transforming polymeric nanoparticles into compacts via NEMs provides stabilization and allows redispersion into original nanoparticles. Despite the reduced redispersibility, compacts loaded with nanoparticles exhibited improved dissolution rate compared with the crystalline drug. Loading of nanoparticles into compacts is a promising approach to overcome the poor stability of nanoparticle within oral drug delivery of nanoparticles.

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years.

Topical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.

Lipid-microparticles for pulmonary delivery of active pharmaceutical ingredients: Impact of lipid crystallization on spray-drying processability

Spray-drying is an extensively used technology for engineering inhalable particles. Important technical hurdles are however experienced when lipid-based excipients (LBEs) are spray-dried. Stickiness, extensive wall deposition, or simply inability to yield a solid product have been associated to the low melting points of LBEs. In this work, solutions containing polyglycerol esters of behenic acid (PGFA-behenates), or other high melting point LBEs, were spray-dried to produce ibuprofen (IBU)-loaded inhalable lipid-microparticles. Prior to spray-drying, rational boundaries for the outlet temperature of the process were defined using LBE-IBU phase diagrams. Despite spray-drying the solutions at outlet temperatures below the boundaries, process performance and yield among LBEs were entirely different. Lipid crystallization into polymorphs or multi-phases negatively impacted the yield (10–47%), associated to liquid fractions unable to recrystallize at the surrounding gas temperature in the spray-dryer. The highest yields (76–82%), ascribed to PGFA-behenates, resulted from monophasic crystallization and absence of polymorphism. Lipid-microparticles, composed of a PGFA-behenate, were characterized by a volume mean diameter of 6.586 µm, tap density of 0.389 g/cm3 and corrugated surface. Application as carrier-free dry powder for inhalation resulted in high emitted fraction (90.9%), median mass aerodynamic diameter of 3.568 µm, fine particle fraction of 45.6% and modified release in simulated lung fluid.

Comparative study of specific activity of rectal suppositories with clopidogrel

One of the most effective platelet antiaggregants is clopidogrel, inhibiting platelet activation by selectively binding adenosine diphosphate (ADP) with specific receptors. However, in a number of clinical situations it is necessary to have a pronounced antithrombotic effect in the shortest possible time which gives rise to interest in the transmucose use of the drug, in particular, rectal route. The theoretical preconditions for the development of a rectal administration of clopidogrel are based on the data that the anti-aggregation effect of a substance is carried out by its main metabolite formed after “first hepatic passage”, while clopidogrel itself in this aspect is inactive. On the base of complex physico-chemical, pharmaceutical, biopharmaceutical, rheological and microbiological investigations, the rational composition of clopidogrel rectal dosage form – suppository on a hydrophilic base to prevent atherothrombotic events in patients with myocardial infarction, acute coronary syndrome, ischemic stroke, peripheral arterial occlusion, is proposed by the employees of the Department of Technology of Medications of the Zaporizhzhia State Medical University. The aim of the work is to investigate the specific activity of rectal suppositories with clopidogrel. Materials and methods. Experimental suppositories with clopidogrel 0,075 g for rectal administration were used as the objects in pre-line studies. The ability of clopidogrel to reduce the inhibitory effect of ADP on adenylate cyclase activity and decrease the number of binding sites for 2-methylthio-ADP (analogue of ADP) without altering the receptor topography is used as a base of the method of comparative study of its specific activity in the rectal dosage form (suppository) and in comparison with the reference medication Plavix (SANOFI WINTHROP INDUSTRIE, France) in the tablet form. Studies were performed on white non-linear rats of different sexes with different mass 150–210 g, aged 3.5–5.0 months. Results. Statistically significant differences in the inhibition of induced platelet aggregation were registered after 6 hours of rectal administration of clopidogrel and gastric administration of the reference medication, indicating the effectiveness of the rectal applicative transmucosal route for this active pharmaceutical ingredient (API). On the 5th day of administration, inhibition of induced platelet aggregation significantly increased, and that is supported by literature on the cumulative effect of clopidogrel in daily life. When comparing the digital material of the table, it is obvious that the rectal administration of clopidogrel is more effective in comparison with oral route which is probably due to the rapid delivery of API to the liver and the formation of an active metabolite of clopidogrel inhibiting the induction and spontaneous aggregation of platelets in human’s and animal’s blood. Obtained data provide with sound arguments for development of rectal suppositories with clopidogrel because in clinical care faster achievement of an anti-aggregation effect in patients with acute coronary syndrome is the primary task of clinical pharmacology and pharmacy. Conclusions. Using the biochemical model of pathology, it was established that the applicative semisolid medication of clopidogrel in the form of rectal suppository exhibited inductive anti-aggregation activity and its administration didn’t reveal any side effects and undesirable events. Rectal suppositories with clopidogrel have been shown to exhibit faster reliable anti-aggregation effect in comparison with intragastric administration.