Injectable Dosage Form Research Articles

Double-layer dissolving microneedles for delivery of mesenchymal stem cell Secretome: Formulation, characterisation and skin irritation study

Regenerative therapy based on stem cells have been developed, focusing on either stem cell or secretome delivery. Most marketed cellular and gene therapy products are available as injectable dosage forms, leading to several limitations requiring alternative routes, such as the intradermal route. Microneedles, capable of penetratingthe stratum corneumbarrier, offer a potential alternative for intradermal delivery. This present study aimed to develop double-layer dissolving microneedles (DMN) for the delivery of freeze-dried mesenchymal stem cell secretome. DMNs were fabricated using a two-step casting method and composed of two polymer combinations: poly(vinyl pyrrolidone) (PVP) with poly(vinyl alcohol) (PVA) or PVP with sodium hyaluronate (SH). The manufactured DMNs underwent assessments for morphology, mechanical strength, in skin dissolution, protein content, in vitro permeation, in vivo skin irritation, and physical stability. Based on evaluations of morphology and mechanical strength, two formulas (F5 and F12) met acceptance criteria. Evaluation of protein content revealed that F12 (PVP-SH combination) had a higher protein content than F5 (PVP-PVA combination), 99.02 ± 3.24 μg and 78.36 ± 3.75 μg respectively. In vitro permeation studies showed that F5 delivered secretome protein by 100.84 ± 0.88%, while F12 delivered 99.63 ± 9.21% in 24 h. After four days of observation onSprague-Dawleyrat’s skin, no signs of irritation, such as oedema and redness, was observed after applying both formulations. The safety of using PVP-PVA and PVP-SH combinations as excipients for DMN secretome delivery has been confirmed, promising significant advancements in biotherapeutic development in the future.

Formulation, Design, Optimization, and Characterization of Novel Long-acting Injectable Dosage Form of Anti-psychotic Drug

Background: The current research aimed to create and analyze a new long-acting Brexpiprazole (BRX) injectable for successful anti-psychotic drug therapy in order to decrease dosage frequency and increase patient compliance. Systems for drug transport to particular body sites or regulating release rates with accuracy are known as drug delivery systems (DDS). By affixing the drug to a carrier particle like liposomes, nanoparticles, microspheres, etc., which modifies the drug's absorption and release properties, using carrier technology, drugs may be delivered in an intelligent manner. Methods: Utilizing Resomer RG 502 H and RESOMER® RG 752 H extended-release Polymer, Using a quasi-emulsion solvent diffusion, microspheres were made, and emulsification and solvent evaporation process. Results: The produced microspheres were assessed for stability tests, in vitro drug release, flow characteristics, and drug entrapment efficiency. FTIR experiments were used to establish how well the drug excipients worked together. The acarbose microspheres that were created had an 89.9 to 96.1 percent drug entrapment efficiency. The impact of factors like polymer content on medication release was studied. The Stability study of the formulation was carried out under different conditions, and data were established. Comparative pharmacokinetic studies between marketed oral formulation and Brexpirazole microsphere test formulations in Wistar/SD Rats were carried out and concluded. Conclusion: Brexpiprazole (BRX) novel long-acting injectable formulation, could be used effectively for the treatment of mentally challenged anti-psychotic patients worldwide.

Correction: The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form

Correction: The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form

The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form

The Novel Quality by Design Concept in the Development and Validation of a Stability-Indicating RP-HPLC PDA Method for Estimating Terlipressin in an Injectable Dosage Form

The study of the range, availability and affordability of vitamin B1 medicines combined with vitamin B6 and/or B12 in the pharmaceutical market of Ukraine

Aim. To conduct a study of the range of combined neurotropic vitamins B in the pharmaceutical market, to analyze their availability and affordability for patients with neurological diseases. Materials and methods. The study was conducted using data from the State Register of Medicines of Ukraine, ATC classification, and information on statistical retail prices from the online service www.tabletki.ua. Such research methods as systematization, generalization, comparative, marketing, content analysis, pharmacoeconomic analysis by the “cost of illness” method were used. Results. The pharmaceutical market of vitamin A11DB group Vitamin B1 in combination with vitamin B6 and/or B12 registered in Ukraine as 43 trade names (TN) of medicines has been analyzed taking into account all dosage forms; among them, 53.5 % are medicines of domestic manufacturers. Among dosage forms, the vast majority are solutions for injection (65.1 %). Only 56 % of the registered medicines are accessible, i.e. available for sale in regional pharmacies, with an equal proportion of domestic and foreign manufacturers. In 63 % of the drugs studied, the price liquidity ratio indicator shows fluctuations from 0.51 to 1.0, which indicates a significant range of drug prices, a relatively low level of competition in the market, and negatively characterizes the availability of these drugs for the population. It has been found that for injectable dosage forms of the drugs studied, the coefficient of adequacy of solvency ranges from 1.41 % to 3.30 %, and for oral medicines – from 0.67 % to 6.20 %, i.e., the cost of purchasing one package of a complex vitamin B medicine does not exceed 6.20 % of the average monthly salary on the example of the Odesa region, which is not included in the List of territories where military operations are (were) conducted or temporarily occupied. A pharmacoeconomic analysis has been conducted using the “cost of illness” method; and the drugs of choice have been selected taking into account the information on their equivalence provided by the manufacturer. According to the results of this analysis, it has been found that the cost of treating polyneuropathy with complex vitamin B medicines produced in Ukraine is 1.4-6 times more affordable than in the case of imported analogues. Conclusions. The results presented indicate the need to introduce additional mechanisms for compensating the cost of vitamin B medicines in order to increase the level of socio-economic affordability of pharmaceutical care provided in pharmacies. In addition, they can be used in the formation of the range of medicines to ensure the availability of medicines of choice, taking into account the most affordable cost of the treatment course.

Skin ‘Bleaching’ Practices and Associated Adverse Health Effects in Zimbabwe: A Canonical Correlational Study of Harare

The study aimed to identify the ingredients, processes and practitioners involved in the skin lightening practices in Zimbabwe and to identify the associated, adverse health effects as well as to establish the user demographics. A technical field survey was carried out in Harare, Zimbabwe from October 2022 to March 2023. Out of a total of 450 potential participants, 382 individuals in 3 broad groups were successfully interviewed; these included 150 skin lightening practitioners and traders, 118 skin lightening products users and 114 individuals who have never practiced skin bleaching. A semi structured technical questionnaire was used for each group of participants and the collected data were analysed qualitatively and quantitatively. The study observed that both sexes are involved in skin lightening in Zimbabwe, the majority (52%) being women aged between 31-45 years. The established industry, is divers, including registered healthcare providers, commercial trade, informal markets and others. The majority of practitioners (65%) have less than 5 practising years. There are over 30 different skin lightening products available either as prescription medications, OTC treatments, commercial products, network marketing products as well as illegal bootleg concoctions. The products extends from creams, lotions and serums, to oral and injectable dosage forms. The most prevalent products being corticosteroid creams. 75% of users reported both reversible and non-reversible adverse health side effects and outcomes including skin irritations, inflammation, rashes, erythema, oedemas, ochronosis, dermal atrophy, photophobia, insomnia and unexplained weight gain. The most prevalent side effect being pruritus and irritations. It was observed that there is no formal registration, regulation or legislation covering the products, processes and practice of skin lightening in Zimbabwe.

Development of injectable upconversion nanoparticle-conjugated doxorubicin theranostics electrospun nanostructure for targeted photochemotherapy in breast cancer.

Nanotheranostic-based photochemotherapies with targeted drug delivery have considerably surfaced in cancer therapy. In the presented work, polyethyleneimine-coated upconversion nanoparticles were engineered to conjugate covalently with doxorubicin. Upconversion nanoparticles (UCNP)-Doxorubicin (DOX)/synthesized epidermal growth factor receptor-targeting peptide blended with polymer composite was electrospun and formulated as the injectable dosage form. The size of the UCNP and the nanofiber diameter were assessed as 26.75 ± 1.54 and 162 ± 2.82 nm, respectively. The optimized ratio of dopants resulted in UCNP photoluminescence with maximum emission intensity at around 800 nm upon 980 nm excitation wavelength. The paramagnetic nature of UCNPs and amide conjugation with the drug was confirmed analytically. The loading capacity of UCNP for doxorubicin was determined to be 54.56%, while nanofibers exhibited 98.74% capacity to encapsulate UCNP-DOX. The release profile of UCNP-DOX from nanofiber formulation ranged from sustained to controlled, with relative enhancement in acidic conditions. The nanofiber demonstrated good mechanical strength, robust swelling, and degradation rate. Biocompatibility tests showed more than 90% cell viability on L929 and NIH/3T3 cell lines with UCNP-DOX@NF/pep nanoformulation. The IC50 values of 2.15 ± 0.54, 2.87 ± 0.67, and 3.42 ± 0.45 μg/mL on MDA-MB-231, 4T1, and MCF-7 cancer cell line, respectively, with a significant cellular uptake, has been reported. The UCNP protruded a ≈62.7°C temperature rise within 5 min of 980 nm laser irradiation and a power density of 0.5 W cm-2. The nanoformulation induced reactive oxygen species of 65.67% ± 3.21% and apoptosis by arresting the cell cycle sub-G1 phase. The evaluation conveys the effectiveness of the developed injectable theranostic delivery system in cancer therapy.

Fucoidan-incorporated dissolving microneedles: A novel approach to anticoagulant transdermal delivery

Cardiovascular disease (CVD) is the leading cause of global mortality, particularly in Indonesia. Vascular disorders, including thrombosis and atherosclerosis, have been implicated as potential contributors to the development and progression of CVDs. Anticoagulant agents, such as heparin, have been commonly used to treat vascular disorders. Nevertheless, this agent may result in a hazardous adverse effect. Bioactive substances like fucoidan (FC) have emerged as an alternative, with anticoagulant and antithrombotic properties similar to heparin. However, FC was often found in oral, injectable, and transdermal dosage forms, which has considerable limitations due to its low bioavailability alongside with poor patient comfort and compliance. To overcome these issues, FC was further incorporated into dissolving microneedles (DMN) that can facilitate transdermal delivery of FC by penetrating the stratum corneum. Fucoidan Dissolving Microneedle (FC-DMN) was fabricated using gelatin and polyvinyl pyrrolidone (PVP) as polymers with various concentrations. Following several evaluations, FC-DMN exhibited good stability, mechanical resistance, and penetration ability. Ex vivo permeation study revealed that 91.23 ± 0.12 % of FC was released from the optimum formula. Furthermore, the hemolytic activity demonstrated that FC-DMN did not induce notably hemolytic, confirming its safe applicability. The in vivo anticoagulant activity test showed increased aPTT and PT values following a 7-day regimen of FC-DMN application. Interestingly, there were no significant differences (p > 0.05) were observed between FC-DMN and heparin injection (dosage 200 IU/Kg). In contrast, significant differences (p < 0.05) were observed when comparing FC-DMN to healthy controls, negative controls, and heparin gel. These findings suggested that FC-DMN offers a promising alternative to conventional anticoagulant therapies and can effectively deliver FC into systemic circulation. This study successfully developed a safe, painless, and nonirritating FC-DMN with promising results for enhancing the efficacy of anticoagulant therapy through the transdermal route.

Determination of quality indicators of a combined nootropic drug

Introduction. The state drug policy of the Republic of Uzbekistan is aimed at the release of new affordable import-substituting drugs of domestic production, which are not inferior in activity to foreign analogues. Taking this into account, and also taking into account the high cost of imported nootropic drugs, the pharmaceutical production of LLC «Тemur med farm», Syrdarya region, Uzbekistan has developed the composition, technology and production of the combined drug "Nootrotem". "Nootrotem" is a combined preparation of piracetam and methylethylhydroxypyridine succinate in an injectable dosage form. Based on preclinical pharmacological studies, the pronounced nootropic and metabolic effects of the studied drug have been proven. Objective: The purpose of these studies is to develop quality assessment methods and establish quality indicators of the combined drug "Nootrotem" solution for infusions. Material and methods. 5 series of laboratory samples of the drug "Nootrotem" solution for infusions obtained at the pharmaceutical production "Temur med farm", Uzbekistan, were used as research objects. Results. The determination of the quality indicators of the studied drug was carried out in accordance with the modern requirements of the National pharmacopoeia of the Republic of Uzbekistan and the European pharmacopoeia, as well as in accordance with the general technical regulations on the safety of medicines. Conclusion. As a result of the conducted research, the main quality indicators of the drug "Nootrotem" solution for infusions were established according to the following indicators: description, authenticity, transparency, chromaticity, pH, package filling volume, mechanical inclusions, impurities, residual sulfur dioxide, osmolality. The limits of their rationing have been established in accordance with the State Budget of the Republic of Uzbekistan.

Current state of research in the field of intranasal dosage forms and the possibility of using piracetam as an intranasal gel

The intranasal method of administration has been known for a long time and until recently was regarded only as a method of local treatment of nasal cavity diseases. However, nowadays it is increasingly being considered as a promising and convenient way to deliver many drugs with a resorptive effect into the body. This is not surprising: this method of administration has a number of advantages and can be used for drugs produced only in the form of injectable solutions. The drug will not be metabolized in the liver, since it will enter the blood directly through the epithelium of the nasal cavity, which is abundantly supplied with blood. In addition, compared with injectable dosage forms, this method is less traumatic and does not require the participation of medical personnel and special training. The use of intranasal dosage forms, primarily for the treatment of cerebral pathologies, is a promising direction in medicine and pharmacy.

Determinants of medication adherence and impact of mobile telephony, pillbox interventions on compliance and glycemic control among patients with type 2 diabetes

Abstract Background: Medication adherence has been linked to improved glycemic control, fewer complications from diabetes, fewer hospitalizations, reduced health care expenses, and a decreased mortality rate. The medication adherence pattern, reason, and factors associated with poor medication adherence among patients living with type 2 diabetes mellitus were determined, and the impact of two interventions to improve medication adherence was assessed. Materials and Methods: The medication adherence patterns of 240 people living with diabetes were determined using the Morisky Green Levine Medication Adherence Scale-4 and categorized into low, medium, and high adherence patterns. Patients with poor medication adherence (low and medium pattern) scores were randomized into short message service (SMS) and pillbox interventions, and the impact of Interventions on compliance and glycemic control was determined. Results: Results demonstrate that 3% of patients living with type 2 diabetes have low, 43% medium, and 54% have high medication adherence patterns. The most common reason cited for non-adherence was (88%) followed by lack of finance (5%) and multiple medications (4%). A positive association of injectable dosage forms, number of drugs, and treatment modalities with adherence was found. SMS and pillbox intervention improved medication adherence among individuals with diabetes who had poor adherence, which translated into good glycemic control. Conclusions: The improvement in drug compliance and glycemic control was found to be equivocal among the SMS and pillbox intervention groups. The inclusion of interventions into the institutional education program and counseling by health care workers will motivate patients to adopt these interventions to improve drug compliance and glycemic control.

Formulation Development and Evaluation of Highly Oxidative Degradative Drug Molecule Injectable Dosage form by Lyophilisation Techniques

Adrenaline (ADR) It is lifesaving and is the only first-line drug for the treatment of anaphylaxis. Adrenaline (ADR) is the endogenous catecholamine with potent alpha- and beta-adrenergic stimulating properties. Alpha-adrenergic action increases systemic and pulmonary vascular resistance, increasing both systolic and diastolic blood pressure. Adrenaline is released in the bloodstream, which increases heartbeat, muscle strength, blood pressure, and glucose metabolism. Oxidation degradation of the medicinal product is the main route of degradation. Affects chemical and physical changes in drugs during the formulation development process. Physicochemical changes in the product can affect both the safety and efficacy of the drug product. Main product development strategy to develop, a stable, freeze-dried product of epinephrine for injection. The stability of adrenaline injection is of paramount objective as it is classified as a catechol compound that is sensitive to oxidation to o-quinone and therefore can react further to form highly colored compounds. Adrenergic drugs further react to form adrenochrome, a highly colored indole derivative. The rate of this reaction increased with pH, temperature and presence of the metal ions. Aqueous solutions of adrenergic agonists decompose rapidly when exposed to air, light, or heat, turning pink due to oxidation to adrenochrome and brown due to melanin formation. Due to its strong oxidizing properties and easy decomposition in aqueous solutions. To achieve this, the aqueous solutions of adrenergic agonists decompose rapidly when exposed to air, light, or heat, turning pink due to oxidation to adrenochrome and brown due to melanin formation. Due to its strong oxidizing properties and easy decomposition in aqueous solutions.

Equilibrium Solubility of Acetaminophen in Ternary Mixtures as a Tool for Design of Concentrated Parenteral Medications

AbstractThe main purpose of this research was to evaluate the mass/volume percentage (%m/v) solubility of acetaminophen (ACP) in {ethanol (EtOH) (1) + propylene glycol (PG) (2) + water (3)} mixtures from 20.0 to 40.0 °C to expand the solubility database of this drug in mixed pharmaceutical solvents useful for designing high concentrated liquid products including injectable solutions. This is because ACP is an analgesic drug widely used available for oral administration as tablets or solutions. Besides, as injectable products, it is only available for perfusion in as 1 g in 100 mL (1.0%m/v). However, it is not available as 5 mL ampules for supplying doses of 500 mg. As demonstrated in this research some cosolvent mixtures allow ACP concentrations higher than 10.0%m/v, for instance the aqueous ternary mixture with 20% w/w of ethanol and 30% w/w of PG, among other possible mixtures. Flask shake method and UV–vis spectrophotometry were used for ACP solubility determinations at different temperatures. ACP solubility results are presented as Cartesian and triangular solubility profiles. ACP solubility increases with temperature arising and the cosolvent proportion in the mixtures. Maximum %m/v ACP solubility value is observed in the aqueous ethanol binary mixture of w1 = 0.80 at all temperatures being 21.18% at 25.0 °C. All the solubility values were well correlated using the Jouyban-Acree model obtaining mean percentage deviations of 3.8% (N = 330). In this way, %m/v equilibrium solubility of ACP in {EtOH + PG + water} mixtures has been studied and correlated at several temperatures as contribution to preformulation studies of injectable homogeneous liquid pharmaceutical dosage forms.

METHOD DEVELOPMENT AND VALIDATION OF UV SPECTROSCOPY FOR THE ESTIMATION OF EPHEDRINE HYDROCHLORIDE IN BULK AND PHARMACEUTICAL FORMULATION

Development and validation of simple, rapid, accurate, precise and sensitive UV-Spectrophotometric method for the estimation of Ephedrine hydrochloride in bulk drug and Injection dosage form was performed in the current research. Quantitative determination of Ephedrine hydrochloride was done using distilled water as a solvent. λmax of Ephedrine hydrochloride in distilled water was measured at 270 nm. Linearity range for Ephedrine hydrochloride was 2-10 μg/mL and coefficient of correlation for Ephedrine hydrochloride was 0.999. Accuracy was performed and the percentage recovery of Ephedrine hydrochloride was found to be in the range of 98.6-99.17. The % relative standard deviation (RSD) for precision was less than 2%, LOD &amp; LOQ was 0.079 μg/mL and 0.24 μg/mL respectively. The results suggest that method can be employed for routine analysis of Ephedrine hydrochloride in bulk drug and in pharmaceutical Dosage form.

FACTORS AFFECTING THE WITHDRAWAL PERIOD OF AMOXICILLIN FROM VETERINARY MEDICINAL PRODUCTS USED IN FOOD-PRODUCING ANIMALS

The withdrawal period of active substance residues from the animal’s body which products are intended for human consumption is an important criterion for the safety of veterinary medicinal products. This products cannot be authorized without establishing this important parameter. There are a number of veterinary medicinal products on the market of Ukraine and EU member states, which have the same active substance in the same concentration and pharmaceutical formulation, but the withdrawal period can differ significantly.&#x0D; The goal of our study was to determine the influence of various factors on the withdrawal period of amoxicillin from single-component oral (powders) and injectable (suspensions, long acting suspensions) dosage forms, which are included in the State Register of Veterinary Medicines of Ukraine and EU product database (UPD).&#x0D; As is known, amoxicillin is widely used for the treatment of infectious diseases in humans and animals, in particular food-producing ones, which are a source of food products intended for human consumption. From the point of the hazard of development acquired antimicrobial resistance when consuming products of animal origin contaminated with residues, the duration of the established withdrawal period is a question of great importance.&#x0D; As shown in the study results, the pharmacokinetic parameters of veterinary medicinal products, in particular bioavailability, as well as clinical characteristics of the disease, have a significant impact on the duration of the withdrawal period. Usually, the withdrawal period depends on the type of dosage form, and the amount and nature of excipients, because oral and injectable pharmaceutical formulations of the same veterinary medicinal product differ in terms of bioavailability from the systemic circulation and the site of injection. It was also defined that the duration of the withdrawal period depends on the amount of the administered dose of the veterinary medicinal product, the treatment duration, the target animal species, fasting conditions (before or after feeding), and the substrates used for feeding (dissolving in water or mixing with feed), analytical methods used to determine active substances or their metabolites, methods of the statistical processing results and differences between individual values established in a group of animals involved in the study.&#x0D; The importance of approving the withdrawal period for generic veterinary medicinal products manufactured by different companies is confirmed by studies carried out by the European Medicines Agency order at the request of the Competent authorities of individual EU countries in connection with the detection of the overestimated residue level compared with the established maximum limits over time, defined as the withdrawal period specified during product authorization.&#x0D; In two cases, changes were made to the Summary of Product Characteristics and package leaflets, regarding the extension of the withdrawal period of amoxicillin from certain tissues and for different target animal species. Marketing authorization holders are recommended to harmonize the withdrawal period for generic products with the established value for the reference veterinary medicinal products.

Rapid environmentally benign label free detection of heparin using highly fluorescent N,S-CDs sensing probe through a turn-on mechanism

Heparin (HEP) is one of the oldest anticoagulant drugs that currently still in widespread clinical use. It lacks chromophore and not easily derivatized due to its hydrophilic nature. In this work we developed a green, selective, and sensitive fluorescence sensor for detection of HEP in its injection dosage forms. The sensor is composed of nitrogen and sulfur co-doped carbon quantum dots (N,S-CDs) semi quenched by Fe3+. The N,S-CDs were prepared using microwave assisted pyrolysis in 3.5 min and exhibited high emission at 425 nm after excitation at 350 nm with high quantum yield of 96%. Owing to the anionic nature of HEP, it could compete with N,S-CDs for Fe3+ complexation resulting in turning-on the quenched fluorescence. This fluorescence enhancement was linear over a concentration range between 6 and 20 μg/mL (R2 = 0.99) with a limit of detection of 1.41 µg/ml. The accuracy and precision of the proposed sensor were indicated by percentage recovery values between 98% −102% and %RSD less than 2, respectively. Furthermore, the proposed sensor was successfully applied for determination of HEP in injection dosage form. The developed sensor showed excellent greenness on analytical eco-scale (score 93%) and GAPI scale.

Pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in rats. Part 1. Single and multiple intravascular and extravascular administration. Testing the hypothesis of linearity of pharmacokinetics

The pharmacokinetics of dimeric dipeptide mimetic of nerve growth factor GC-2 in the rat blood plasma after different routes of administration was studied. The drug was administered at dose of 150 mg/kg by single and repeatedly. After single intravenous and intraperitoneal injection, GC-2 was detected for 2 h, its half-life was 0.4 h. GC-2 absolute bioavailability after single intraperitoneal injection was 84.62 %, that indicates the prospect of development its injectable (intramuscularly) dosage form. After 4-fold (1.5 h dosing interval) intraperitoneal injection dose-independent pharmacokinetic parameters of GC-2 practically do not change compared to single administration. This indicates that GC-2 is not accumulated in the body of rats. The hypothesis of the linearity of the pharmacokinetics of GC-2 in the rats blood plasma after single intraperitoneal administration at doses of 50, 100 and 150 mg/kg was tested. It was found that the kinetics of GC-2 in the rat blood plasma is linea.

Formulation Development and Evaluation of Freeze-dried Aviptadil Injection using Mannitol as Cryoprotectant

physiological effects that have been well-documented, including anti-inflammatory, immune-modulatory, anti-hypertensive, enhancement of cardiac contractility, vasodilation, and fostering immune-neuroendocrine connection. Aviptadil (AVP) is the name of the vasoactive intestinal polypeptide’s synthetic version. Aims and Objectives: The main goal of this work was to create a novel, stable, lyophilized version of aviptadil injection. The stability of aviptadil is of utmost importance due to its classification as a polypeptide, recommended storage condition of -20°C, and susceptibility to degradation in aqueous solutions. To achieve this, the aviptadil injection was processed using freeze-drying technology with the addition of mannitol, serving as a bulking and cryoprotectant agent, within an aqueous solvent system. The choice of cryoprotectant and solvent system was based on factors such as the drug substance’s solubility, stability, and feasibility in the manufacturing process. During the development of the formulation, the bulk solution underwent evaluation to assess the effects of process time, temperature, and compatibility with the materials it came into contact with. Results and Discussion: The incorporation of mannitol, a sugar alcohol, led to the stability of the bulk solution for up to 24 hours before lyophilization when stored at temperatures between 2 and 8°C. Moreover, enhanced stability was observed post freeze-drying. The lyophilization process was meticulously optimized, taking into account critical quality attributes such as description, active drug content, pH of the reconstituted solution, reconstitution time, moisture content, and color absorption percentage. The bulk solution demonstrated compatibility with various materials employed in manufacturing the drug product, such as stainless-steel vessels, polyethersulfone (PES) and polyvinylidene difluoride (PVDF) membrane filters. Notably, when the drug product bulk solution was kept refrigerated for up to 24 hours, there were no appreciable changes in the critical quality features found. The optimized freeze-dried product successfully meets the quality target product profile (QTPP)’s preset acceptance criteria. Conclusions: The stabilization of AVP injection was successfully achieved through the implementation of the lyophilization process with mannitol as the cryoprotectant. The envisaged injectable formulation proves to be safe and showcases its economic viability, convenience, and overall safety in the preparation methods. These findings strongly support the viability of the freeze-dried formulation as a technically sound solution for ensuring the stability of aviptadil as a drug substance within the freeze-dried injectable dosage form. This formulation warrants more research due to its potential to treat patients with conditions such acute respiratory distress syndrome, acute lung injury, pulmonary fibrosis, and sarcoidosis.

Green and Smart Quantitative Quality Control for Veterinary Mixture of Ivermectin and Clorsulon; Ecological Evaluation of Spectral Analyses via Analytical Eco-Scale, Green Analytical Procedure Index and Analytical GREEnness Metric Approaches.

Global financial market is still highly threatened by bovine fasciolosis; a parasitic infection, that targets cattle, mainly in tropical regions. Binary combination of Ivermectin (IVER) and Clorsulon (CLO), in challenging concentration ratios, is typically indicated for treatment and control of fasciolosis. Present study aims at smart simultaneous spectrophotometric assay of both compounds at their high ratio in marketed formulation and synthetic mixtures, without any prior separation. Furthermore, their greenness profile was evaluated and compared with previous reported assay methods including the official one. Mathematical-based proposed methods are Dual wavelength, Induced Dual wavelength and First Derivative Ratio methods. Each is developed, optimized and applied to determine simultaneously IVER and CLO at linear ranges of 1-30 and 5-40 μg/mL, respectively. They have been validated according to ICH guidelines. Statistical student t- and F-tests, compared the proposed methods with USP chromatographic technique. Ecological appraisal is accomplished using three independent metrics; Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical GREEnness Metric Approach (AGREE). Satisfactory recoveries, ICH compliance and adherence of proposed methods to the ecological safety margin are achieved. Developed methods are eco-friendly, cost effective and can accomplish a routine quantitative quality control for concurrent determination of both drugs. Veterinary antimicrobials need analytical quality control using safer and green methodologies. Data manipulated spectral analyses of IVER and CLO, in ratio 1:10%v/v, is developed and optimized. AES, GAPI and AGREE approaches illustrate the high green compliance in respect to literary reported assays. Furthermore, the United States Pharmacopeia (USP) assay for IVER and CLO in injectable dosage form depends on analysis of each drug separately in the presence of the other drug but it cannot determine both drugs simultaneously at the same time.

A novel formulation enabled transformation of 3-HIV drugs tenofovir-lamivudine-dolutegravir from short-acting to long-acting all-in-one injectable.

To develop an injectable dosage form of the daily oral HIV drugs, tenofovir (T), lamivudine (L), and dolutegravir (D), creating a single, complete, all-in-one TLD 3-drug-combination that demonstrates long-acting pharmacokinetics. Using drug-combination-nanoparticle (DcNP) technology to stabilize multiple HIV drugs, the 3-HIV drugs TLD, with disparate physical-chemical properties, are stabilized and assembled with lipid-excipients to form TLD-in-DcNP . TLD-in-DcNP is verified to be stable and suitable for subcutaneous administration. To characterize the plasma time-courses and PBMC concentrations for all 3 drugs, single subcutaneous injections of TLD-in-DcNP were given to nonhuman primates (NHP, M. nemestrina ). Following single-dose TLD-in-DcNP , all drugs exhibited long-acting profiles in NHP plasma with levels that persisted for 4 weeks above predicted viral-effective concentrations for TLD in combination. Times-to-peak were within 24 hr in all NHP for all drugs. Compared to a free-soluble TLD, TLD-in-DcNP provided exposure enhancement and extended duration 7.0-, 2.1-, and 20-fold as AUC boost and 10-, 8.3-, and 5.9-fold as half-life extension. Additionally, DcNP may provide more drug exposure in cells than plasma with PBMC-to-plasma drug ratios exceeding one, suggesting cell-targeted drug-combination delivery. This study confirms that TLD with disparate properties can be made stable by DcNP to enable TLD concentrations of 4 weeks in NHP. Study results highlighted the potential of TLD-in-DcNP as a convenient all-in-one, complete HIV long-acting product for clinical development.