Oral Formulations Research Articles

Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study.

The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience. We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties. The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables. The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.

FORMULATION AND CHARACTERISATION OF RISEDRONATE SODIUM SUBLINGUAL SPRAY

Objective: To formulate a propellant-free sublingual spray of Risedronate sodium, addressing issues of gastrointestinal side effects associated with current oral formulations and improving patient compliance. Methods: Initially, a fractional factorial design was used to screen variables, followed by a face-centered central composite design for optimization. Formulation batches were characterized by spray pattern, spray angle, leak test, prime test, drug delivery uniformity, drug content per spray, and ex-vivo permeation study. Results: The optimized batch O1 exhibited an ovality ratio of 1.1, a spray angle of 640, and a drug permeation percentage of 4. In vivo absorption analysis revealed that the relative bioavailability of optimized batch O1 was 2.27 times higher than that of the plain drug solution. Compatibility of the product pack with excipients and the drug was confirmed through stability studies of batch O1. Conclusion: The study concluded that Risedronate sodium sublingual spray presents a promising alternative to oral administration, potentially reducing gastrointestinal side effects and enhancing patient compliance.

The Single-Dose Pharmacokinetics of a Compounded Levetiracetam Formulation and Bioequivalence to a Commercial Formulation in Healthy Dogs.

Levetiracetam (LEV) is an anti-epileptic drug used extra-label in dogs. Commercially available extended-release formulations (LEV-ER), administered twice daily, cannot be crushed or split, limiting their use in small dogs. A compounded LEV-ER formulation (PO-COMP) can purportedly be partitioned without loss of extended-release properties. The aims of this study were to establish the pharmacokinetic parameters of PO-COMP, divided at the tablet score, and determine the bioequivalence of partitioned PO-COMP to an intact commercially available Food and Drug Administration-approved human oral generic formulation of LEV-ER (PO-COMM). In a randomized crossover design, 12 healthy dogs received a single IV dose (30 mg/kg) of IV-COMM, a single oral dose (500 mg) of intact PO-COMM, or a single oral dose (500 mg) of partitioned PO-COMP and underwent serial measurement of plasma LEV concentrations over 24 h. PO-COMP was bioequivalent to PO-COMM using the 90% confidence interval method for maximum concentration (-3.2% difference [CI -7.4% to -1.1%]) and area under the curve (-14.4% difference [CI -17.8% to 10.8%]). PO-COMP may improve medication adherence and seizure control relative to immediate-release LEV, which requires three times daily dosing. Efficacy studies of PO-COMP are warranted.

HIV pre-exposure prophylaxis programmatic preferences among people who inject drugs: findings from a discrete choice experiment.

Pre-exposure prophylaxis (PrEP) holds promise for decreasing new HIV infections among people who inject drugs (PWID), yet daily oral PrEP use is low, and PrEP modality and delivery strategy preferences in this population remain understudied. From May 2022-June 2023, we conducted a discrete choice experiment (DCE) with PWID in San Diego, California. Participants viewed 18 PrEP program scenarios in sets of three and chose their preferred scenario within each set. Scenarios consisted of various combinations of five characteristics: PrEP modality (injectable, implantable, oral), frequency of use (annual, bi-monthly, daily), service location (community-based organization, clinic, telemedicine), prescription access location (on-site, street outreach, mail), and adherence supports (social support, outreach worker, phone/text reminder). Multinomial logit regression estimated probabilities of choosing PrEP program scenarios as a function of the five characteristics to estimate part-worth utility scores (PWUS; reflecting relative preferences for specific characteristic values) and relative importance scores (RIS; reflecting the relative influence of each characteristic on program choice). We also explored differences by hypothesized modifiers of preferences (i.e., sex assigned at birth, housing status, injection frequency, prior PrEP awareness). Among 262 participants, mean age was 43.1 years, and most reported male sex assigned at birth (69.5%), identified as non-Hispanic (60.3%), and were previously unaware of PrEP (75.2%). Frequency of use (RIS: 51.5) and PrEP modality (RIS: 35.3) had the greatest influence on PrEP program choice. Within these characteristics, participants had relative preferences for annual use (PWUS: 0.83) and oral PrEP (PWUS: 0.57), and relative aversions to daily use (PWUS: -0.76) and implantable PrEP (PWUS: -0.53). Generally, participants did not indicate preferences for specific service or prescription access locations, or adherence supports; however, among those with prior PrEP awareness, prescription access location and adherence supports had a slightly greater influence on PrEP program choices. Our study considered diverse PrEP scenarios and highlighted potential preferences for long-acting oral modalities. Although not currently available, renewed investment in long-acting oral PrEP formulations may facilitate PrEP care engagement among PWID. Additional delivery and implementation strategy research is needed to support PrEP uptake and persistence in this population.

Fabrication of an In Situ pH-Responsive Raloxifene-Loaded Invasome Hydrogel for Breast Cancer Management: In Vitro and In Vivo Evaluation

Background/Objectives: Raloxifene (RLF) is a therapeutic option for invasive breast cancer because it blocks estrogen receptors selectively. Low solubility, limited targeting, first-pass action, and poor absorption are some of the challenges that make RLF in oral form less effective. This study aimed to create an intra-tumoral in situ pH-responsive formulation of RLF–invasome (IPHRLI) for breast cancer treatment, with the goals of sustaining RLF release, minimizing adverse effects, and enhancing solubility, bioavailability, targeting, and effectiveness. Methods: Numerous RLF–invasome formulations were optimized using design expert software (version 12.0.6.0, StatEase Inc., Minneapolis, MN, USA). Integrating an optimal formulation with an amalgam of chitosan and glyceryl monooleate resulted in the IPHRLI formulation. In vivo testing of the IPHRLI formulation was conducted utilizing the Ehrlich cancer model. Results: Requirements for an optimum RLF–invasome formulation were met by a mixture of phospholipids (2.46%), ethanol (2.84%), and cineole (0.5%). The IPHRLI formulation substantially sustained its release by 75.41% after 8 h relative to free RLF. The bioavailability of intra-tumoral IPHRLI was substantially raised by 4.07-fold compared to oral free RLF. Histopathological and tumor volume analyses of intra-tumoral IPHRLI confirmed its efficacy and targeting effect. Conclusions: the intra-tumoral administration of the IPHRLI formulation may provide a potential strategy for breast cancer management.

C-Phycocyanin and Phycocyanobilin as a Novel Adjuvant in Hepatitis B Vaccine

Background: Vaccine adjuvants are components that enhance immune responses to an antigen. Given the importance of adjuvants, research on novel adjuvants with higher efficacy and fewer adverse effects remains crucial. Spirulina (Arthrospira sp.), an aqueous, photosynthetic, filamentous, spiral, multicellular microalga also classified as a cyanobacterium, is well known for its high protein content, vitamins, essential fatty acids, and amino acids. C-phycocyanin (C-PC) is one of the most significant proteins in Spirulina. Objectives: This study aimed to investigate the adjuvant capabilities of three Spirulina-derived substances—Spirulina extract, C-phycocyanin (C-PC), and phycocyanobilin (PCB)—in conjunction with the Hepatitis B surface antigen (HBsAg). Methods: Vaccine groups received the vaccine and adjuvants three times at two-week intervals, administered either orally or by injection in encapsulated or naked forms. To use the injectable form while preventing antigenic effects from the C-PC protein portion, the PCB portion was isolated and used as an injectable adjuvant. Results: The highest levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) stimulation were observed in the naked PCB form with the vaccine. In both oral and injectable forms of PCB and C-PC, results indicated an increased expression of Hepatitis B surface antibodies (HBsAb) in response to the antigen. The absence of a significant difference between C-PC and Spirulina extract in oral form suggested that the adjuvant effect of this microalga was primarily due to the C-PC compound. Additionally, the injectable form of PCB led to the highest HBsAb expression level. This enhancement of the humoral immune response indicated that these compounds have potential as adjuvants in both oral and injectable forms. Conclusions: These findings suggest the potential for improved Hepatitis B vaccine efficacy with this novel adjuvant, paving the way for further evaluation with other vaccines.

Evaluating pediatric antimicrobial dosing of β-lactam antibiotics for upper respiratory tract infections in emergency and primary care settings.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Pediatric prescribing is often weight and indication specific and has been associated with high rates of error. The aim of this study was to evaluate outpatient β-lactam suspension dosing practices for pediatric upper respiratory tract infections (URIs), to characterize the rate of error and to describe common error types. This retrospective cohort study was conducted at a community health system with 2 emergency departments and 20 outpatient family medicine practices. Pediatric patients treated from these settings with oral suspension formulations of amoxicillin, amoxicillin/clavulanate, cefdinir, or cephalexin for streptococcal pharyngitis or otitis media between June 1, 2020, and May 31, 2023, were eligible for inclusion. Doses were evaluated against indication-specific best-practice guidelines and assessed for guideline concordance. Of the 200 patients evaluated, 100 were treated for streptococcal pharyngitis and 100 were treated for otitis media. Of the prescribed β-lactam doses, 32% were discordant with best-practice guideline recommendations. Dosing errors were more common for pharyngitis than for otitis media (47% vs 17%; P < 0.001). Overdosing was the most frequently observed error in pharyngitis prescriptions (93.6% of errors) and most commonly occurred in patients weighing more than the 20-kg weight associated with the dosing maximum (80.9% of overdosing errors). All patients receiving an inappropriate dose for otitis media were underdosed. Outpatient pediatric dosing errors for URI indications are common among both emergency medicine and family medicine prescribers. Patients weighing over the weight corresponding to the dosing maximum are at highest risk for error. Antimicrobial stewardship interventions targeting the point of prescribing are urgently needed to provide safe dosing practices for pediatric patients.

Medicines shortages in the UK: review of the causes and analysis of serious shortage protocols – a mixed methods study

Abstract Introduction Causes of medicines shortages are multifactorial. In February 2019, the Human Medicines Regulations 2012 introduced Serious Shortage Protocols (SSPs) to address medicines shortages. SSPs are issued by the Department of Health and Social Care and enable pharmacists to supply alternative medicines without amended prescriptions1. Aim This review aimed to explore contemporary reasons attributed to medicines shortages in the United Kingdom (UK) and analyse expired SSP records. Methods A rapid scoping literature review was conducted using National Library of Medicine (PubMed®) and Elsevier (ScienceDirect). Grey literatures were collated from the Pharmaceutical Journal, Google, and Public Health England’s grey literature index. Searches were limited to publications written in English, published since 2014, which met the inclusion criteria (medicines OR drugs AND shortages AND causes). Data extraction and analysis was performed using Microsoft Excel. Expired SSPs were extracted to Microsoft Excel and analysed using descriptive and inferential statistics on R software (v.4.3.2). SSP data is publicly available; therefore, no ethical approval was required. Results Causes of Medication Shortages A total of 11 papers were selected, in which 77 medicines shortage causes were discussed. Narrative analysis identified 10 shortage-drivers. The most frequent were Manufacturing and Quality Challenges (30%,23/77), Business and Commercial Issues (21%,16/77), and Regulatory Changes and Challenges (10%,8/77). Content analysis found that supply-driven issues were more frequently cited than demand-driven issues. SSP Analysis Between October 2019 and June 2024, 59 SSPs had expired2. Menopausal Hormonal Treatments (MHTs) were the most common medication class in shortage (41%,24/59), followed by antibiotics (17%,10/59), and antidepressants (12%,7/59). The mean shortage length was 129.2 days (IQR=51–196), the longest lasting 359 days (oestradiol 0.5mg/1mg gel sachets). Oestradiol transdermal medications accounted for 19 of 24 MHT SSPs. The mean MHT shortage length was 152.6 days (IQR=51.0–216.0). Phenoxymethylpenicillin accounted for 8 of 10 antibiotic shortages. All 8 phenoxymethylpenicillin SSPs were active from 15 December 2022 to 12 May 2023; 7 of 8 were oral solution formulations. The mean antibiotic shortage length was 168.8 days, which is significantly longer than the whole sample average (p&amp;lt;0.05, IQR=147.0–148.0). All antidepressant SSPs were fluoxetine capsules. The mean shortage length was 99 days (IQR= 35.5–122.0). Discussion Existing literature suggests supply-driven rather than demand-driven causes of medication shortages are more pertinent; however, most expired SSPs were issued in response to demand-driven factors, such as disease outbreaks and changing prescribing demand. This suggests the extent of demand-driven shortages is not reflected in current literature. Future research should explore how demand-driven causes of shortages can be mitigated. As a rapid scoping review was conducted, the full breadth of literature may not be presented. Additionally, the grey literature findings are limited by potential inaccuracies. Finally, the use of narrative analysis may limit the generalisability of identified shortage drivers. As of 05 June 2024, there are 5 active SSPs. With medicines shortages becoming normalised within the UK health system3, there is an urgent need to mitigate supply- and demand-driven causes. Additionally, further research should explore why certain medication classes are more frequently in shortage than others.

Formulation and Evaluation of Colon Specific Meloxicam Microcapsules for the Treatment of Arthritis

Objective: The main objective of the current study was to formulate and evaluate meloxicam-loaded microcapsules for colon-specific drug delivery using pH-dependent polymers. The emerging need for developing sustained release NSAIDs to minimize the dosing frequency was the main concern. Consequently, creating an oral sustained release formulation for the treatment of arthritis may be one method to get around this. Methods: Eudragit RS/RL-100 polymers were used in emulsion solvent evaporation processes to create Meloxicam (MLX) microcapsules. Compatibility tests (FTIR), surface morphology by Scanning Electron Microscopy (SEM), yield, drug content, entrapment efficiency, and in vitro dissolution studies were performed on the produced MLX microcapsules. Results: There was no interaction between the polymer and MLX, according to the IR spectra. The microcapsules were spherical in nature, which was confirmed by SEM. Normal frequency distribution MLX microcapsules were produced. The maximum drug entrapment efficiency of 94% was attained. The in vitro performance of MLX microcapsules demonstrated that the polymer concentration influenced sustained release. Furthermore, it was observed that the amount of polymer utilized regulated the release of the drug. Conclusion: Based on the findings, it was concluded that one of the most promising formulation methods for creating colon specific drug delivery systems for the treatment of arthritis is the production of MLX microcapsules.

Application of nucleophilic substitution reaction for sensitive determination of heptaminol hydrochloride in pharmaceuticals

A straightforward and sensitive spectrofluorimetric approach was established for the determination of heptaminol hydrochloride (HTM-HCl) based on the derivatization of the drug through its reaction with 5-dimethylaminonaphthalene-1-sulfonyl chloride (Dansyl chloride). The reagent underwent a nucleophilic substitution of its chlorine atom with HTM to give N-(5-dimethylaminonaphthalene-1-sulfonyl)-6-amino-2-methylheptan-2-ol. The highly luminescent derivative was extracted using methylene chloride and subjected to analysis at an excitation wavelength of 345 nm and an emission wavelength of 490 nm. The chemical reaction occurred within an aqueous environment buffered with a 0.1 M borate buffer solution adjusted to pH 10.5. Experimental findings indicate that the proposed method displays sensitivity and linearity across a concentration range from 0.03 to 2 µg mL− 1. The method achieves lower detection and quantification limits of 0.016 and 0.048 µg mL− 1, respectively. The analytical validation of this method followed the guidelines outlined by the International Council of Harmonization (ICH). This approach was applied effectively for quantifying the medication in both tablet and oral drops formulations available on the market, demonstrating excellent recovery of 98.95 ± 0.45 for tablets and 99.37 ± 0.24 for oral drops with no interference from excipients.

Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial.

Realgar-Indigo Naturalis Formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of 6 cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of two-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively. (The ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, (P < .01), with a percentage difference of -1% (95%CI, -4.8 to 6.9). No deaths have been observed. Most adverse events were moderate. This study confirms the noninferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy. (ClinicalTrials gov. Identifier: as NCT02899169).

Glucagon-like peptide-1 receptor agonists for treatment of diabetes and obesity: advantage of oral delivery

GLP-1 receptor agonists ((GLP-1 RAs) are currently receiving a lot of attention because of their impact in diabetes, weight loss and other areas. While GLP-1 RAs in injectable form are highly efficacious, further work is required to develop oral versions which can deliver these peptides efficiently without requiring use of excessively high doses. This paper describes the ability of an oral peptide delivery formulation, Axcess™, to enhance uptake of GLP-1 receptor agonists via the intestine, resulting in changes in insulin and glucose blood levels indicative of biopotencies of 9% for exendin-4 and 14.8% for semaglutide in preclinical models. The route of delivery suggests that the peptides will be able to interact with the GLP-1 receptors on the vagal afferents of the intestine, as is the case for native GLP-1 in healthy individuals. GLP-1 receptor agonists administered via this route will be a valuable addition to the therapeutic modalities available for treatment of diabetes and obesity.

Real-World Comparison of Oral Versus Injectable Semaglutide for the Reduction of Hemoglobin A1C and Weight in Patients with Type 2 Diabetes.

No head-to-head comparisons of semaglutide formulations currently exist in the literature. In practice, many may think that oral and injectable semaglutide formulations are interchangeable, although there is currently limited real-world data to determine whether this is accurate. The purpose of this study was to determine the effect of oral versus injectable semaglutide on hemoglobin A1C (HbA1C) and weight in patients with type 2 diabetes (T2D). This was a retrospective single-center review of adult patients who had a diagnosis of T2D and were treated with oral or injectable semaglutide between November 1, 2019, and July 31, 2022. Primary outcome was a comparison of changes in HbA1C (%) and weight (kg) from baseline to 6 months between patients receiving oral versus injectable semaglutide, stratified according to highest dose received. Secondary outcomes included frequency of dose reductions and discontinuations, achievement of clinical goals, and presence of an embedded clinical pharmacist at patients' primary care office. A total of 105 patients were included. Patients experienced mean decreases in HbA1C and weight from baseline to 6 months of -1.75% (P < 0.001) and -3.64 kg (P = 0.015), respectively, in the oral semaglutide group and -1.35% (P < 0.001) and -5.26 kg (P < 0.001), respectively, in the injectable semaglutide group. When directly comparing semaglutide formulations, oral semaglutide demonstrated a 0.4% greater numerical reduction in HbA1C (P = 0.523) and injectable semaglutide demonstrated a 1.62-kg greater numerical reduction in weight (P = 0.312). Adverse events (AEs) occurred more frequently with oral semaglutide than with injectable semaglutide (16.7% vs 4.9%). Discontinuation due to AEs was more common with oral semaglutide. In this study, patients with T2D who received oral semaglutide demonstrated greater reductions in HbA1C, whereas those treated with injectable semaglutide had greater reductions in weight, although there were no statistically significant reductions in HbA1C or weight between the 2 formulations. Rates of AEs and discontinuation were more common in the oral semaglutide group.

A Spray-Dried Self-Stabilizing Nanocrystal Emulsion of Traditional Chinese Medicine: Preparation, Characterization and ex vivo Intestinal Absorption

AbstractSalvia miltiorrhizae (Danshen, the rhizome of Salvia miltiorrhiza Bge.) and Chuanxiong rhizome (Chuanxiong, the rhizome of Ligusticum chuanxiong Hort.) are two traditional Chinese medicines that have been widely used for the treatment of cardiovascular and cerebrovascular diseases. However, formulation development is difficult due to the complexity of the active ingredients, particularly the water-insoluble tanshinones and volatile oil of Chuanxiong rhizome, which cannot be absorbed via oral administration in conventional dosage forms. This study aimed to develop a self-stabilized nanocrystal emulsion co-loading the water-soluble, insoluble, and volatile active ingredients of Salvia miltiorrhizae and Chuanxiong rhizome to improve the bioavailability of the drugs. In this work, a high-pressure homogenization method was used to prepare a self-stabilizing nanocrystal emulsion. The emulsion was then spray-dried using hydroxypropyl-β-cyclodextrin. The dispersibility and storage stability of the spray-dried emulsion, the particle size and morphology of the emulsion droplets, and the drug content and phase distribution of the reconstituted emulsion were evaluated. An everted intestinal sac model was established, and high-performance liquid chromatography was used to determine the concentration of six active components (ferulic acid, salvianolic acid B, senkyunolide A, ligustilide, cryptotanshinone, and tanshinone IIA) and to assess the cumulative uptake amount of the drug and the apparent permeability coefficient. A mixture of the crude materials of tanshinones extract, total salvianolic acid, ferulic acid, and volatile oil of Ligusticum Chuanxiong was used as a control. The results showed that the spray-dried emulsion can be easily reconstituted into a uniform submicron emulsion with no significant changes in particle size, morphology, and microstructure of the emulsion droplets compared with the original emulsion before drying. The self-stabilizing nanocrystal emulsion significantly improved the intestinal absorption of water-insoluble components (tanshinone IIA, cryptotanshinone, and ferulic acid), and volatile oil components (senkyunolide A and ligustilide). Overall, the spray-dried self-stabilizing nanocrystal emulsion represents a potential oral formulation for Salvia miltiorrhiza and Chuanxiong rhizoma.

Assessment of the Bangladeshi Antibiotic Market: Implications of the WHO AWaRe Classification and Dosage Form Availability on Antimicrobial Resistance

BackgroundAvailability of antibiotics without prescription contributes to the rising threat of antibiotic resistance due to widespread self-medication and improper use. In this study, we aimed to assess the antibiotic market in Bangladesh according to the WHO AWaRe (Access, Watch, Reserve) classification system to better understand how the unregulated access of antibiotics may influence self-medication practices and the emergence of antibiotic resistance in the country. MethodsData on AWaRe class antibiotics, their strengths, and dosage forms were collected from Bangladeshi drug indexing smartphone applications, the Bangladesh National Formulary (BDNF), and the Directorate General of Drug Administration (DGDA) website. Sales data were analyzed using IQVIA data to determine the market value and compound annual growth rates (CAGR) of antibiotics. The analysis focused on categorizing antibiotics according to the WHO AWaRe classification and examining their availability in various dosage forms and strengths including child-appropriate formulations. ResultsOf the 81 antibiotics available in Bangladesh, 54.32% belong to the Watch class, 30.86% to Access, 8.64% to Reserve, and 6.17% were unclassified. In terms of ATC classifcation, the majority (91.35%) belonged to the J01 class. Most antibiotics were available in multiple dosage forms and strengths, with tablets (54.87%), injections (48.78%), and capsules (30.48%) being the most common. Additionally, 35.8% of antibiotics were available as child-appropriate formulations. Oral formulations were prevalent, with 88.0% of Access, 75.0% of Watch, and 28.57% of Reserve class antibiotics were available in oral dosage forms. A total of 56 antibiotic combinations were identified, including six WHO-recommended and two WHO-not-recommneded fixed-dose combinations. Watch class antibiotics dominated the market in terms of sales value and CAGR. ConclusionThe widespread availability of Watch class antibiotics, particularly in oral and child-appropriate formulations suggest a need for stricter regulation and public health interventions to curb self-medication, inappropriate marketing and use of antibiotics to mitigate the risks of resistance.

A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intraabdominal infections

ObjectiveTo demonstrate the noninferiority of intravenous (IV) sulopenem to IV ertapenem, each followed by an oral regimen, in adults with complicated intraabdominal infections (cIAI). MethodsHospitalized adults with cIAI were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid twice daily or 5 days of IV ertapenem followed by oral ciprofloxacin/metronidazole or amoxicillin-clavulanate depending on baseline pathogen susceptibility. The target treatment duration was 7-10 days. The primary (FDA-specified) endpoint was clinical response at Day 28 [Test-of-Cure (TOC)] in the micro-Modified Intent to Treat (micro-MITT) population. Results674 patients were randomized. The two treatment arms were well-balanced. E. coli (395 patients) and B. fragilis (111 patients) were the most frequently isolated pathogens. Clinical success rates in the micro-MITT population were 81.9% (204/249) for sulopenem-treated patients and 87.9% (233/265) for ertapenem-treated patients. The lower bound of the confidence interval (CI) for the treatment difference of the primary endpoint was below the prespecified non-inferiority margin of -10.0 [treatment difference -6.0%, 95% CI [-12.2, 0.2]. In all other analysis populations, the lower limit of the 95% CI was above -10.0. Treatment emergent adverse events (all, 26.0% [87/335] vs 23.4% [78/333]; related, 6.0% [20/335] vs 5.1% [17/333]) were similar for sulopenem and ertapenem, respectively. Most events were mild to moderate in severity. There were more serious adverse events in the sulopenem arm (7.5% [25/335] vs 3.6% [12/333]), only two of which were considered possibly drug-related. ConclusionsSulopenem IV followed by oral sulopenem etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down in treating cIAI in the micro-MITT population. This finding should be interpreted in the context of country regulations, as endpoint timing, primary analysis population and noninferiority margin may vary regionally. Both IV and oral sulopenem were well-tolerated; the oral formulation allowed patients with resistant pathogens to step down from IV therapy. Clinical Trial RegistrationNCT03358576.

P011 Evaluation of oral nano-silymarin formulation efficacy as an adjuvant to chemotherapy for non-metastatic prostate cancer

P011 Evaluation of oral nano-silymarin formulation efficacy as an adjuvant to chemotherapy for non-metastatic prostate cancer

Understanding the effect of plasticizers in film coat materials on the physical stability of amorphous solid dispersions

Amorphous solid dispersions (ASDs) have been extensively utilized to improve the bioavailability of drugs that have low aqueous solubility. The influence of different excipients on the conversion of amorphous drugs into their crystalline forms in ASDs has been extensively researched. However, there is limited knowledge examining the impact of film coating materials on the physical stability of oral tablet formulations containing ASDs. In this study, we demonstrate that plasticizers present in film coats can have a detrimental impact on the physical stability of ASDs. We systematically compared two frequently used plasticizers in film coats: triacetin and polyethylene glycol 3350 (PEG 3350). To gain mechanistic insights into the detrimental effects of plasticizers on the physical stability of ASDs, plasticizer leaching studies and physical stability studies of solvent-evaporated and spray-dried intermediates (SDI) using two BCS class II drugs were conducted. Triacetin was found to leach into the tablet core within one week when stressed at 40°C/75% RH, whereas no leaching was observed for PEG 3350, as discerned from spectroscopic studies. We also found that triacetin-containing ASDs exhibited greater amorphous to crystalline form conversion of the drug compared to PEG 3350-containing ASDs after stability testing. Moreover, the incorporation of triacetin into polymers was found to cause a significant depression of glass transition temperature and upon equilibration with moisture, a drop below room temperature. Overall, these observations underscore the importance of carefully selecting plasticizers to be present in film coatings when developing ASD pharmaceutical products.

Various drugs used in oral disintegration tablet formulation

Oral drug administration is more widely accepted because it is used to provide between 50 and 60 percent of medications. The solid dosage forms are commonly utilized since they are simple to administer, precise in their dosage forms, beneficial for self-medication, and preventive of discomfort, and last but not least, the excellent level of patient adherence. The capsules and tablets are the most widely used solid dose form administered orally. Aside from ingesting it does not possess any noteworthy drawbacks. Water plays a crucial function in this swallowing process. Even following this, some people had difficulty swallowing. In order to prevent these issues, mouth dissolving tablets were developed. They have the benefit of not requiring water and don't require swallowing because they dissolve or disintegrate in saliva. In light of the design it began to behave in two ways: first, some tablets disintegrated quickly, taking just a few moments in saliva. Another kind of tablet is known as a "first disintegration tablet" since it contains some substances that slowed down the tablet's rate of breakdown. Review attention was drawn to the concise talk about mouth dissolving tablets and the most recent versions available.

Maharashtrian Dalit Jalse as an Inspiration to Anti-caste Movements: A Reply from Subaltern to Subalternity

This article focuses on the Maharashtrian Dalit representation in the popular traditional art form of jalsa and aims to know how Marathi Dalit rangbhoomi/theatre has been used as a source to present stereotypical Dalit untouchability and caste-based issues. A long history of Dalit art from the 1930s to the twenty-first century has been transformed into a creative form for social awakening. Various forms of jalse (like ‘ Amberkarite jalse’ and ‘ Amberkarite Shahiri’, Powade, Ovi or Lavani later became mostly part of Ambedkari jalse) and their response to subalternity have a significant role in inspiring anti-case movements. These forms have influenced Dalit artists and activists not only in Maharashtra but also across India. Visiting the history of Dalit rangbhoomi demonstrates subalterns’ response to a Dalit subalternity. In addition, this study is very substantial to touch on the uncovered area of Dalit jalse and Qawwali as an anti-caste movement. Only countable articles have been published in English on Maharashtrian jalse. Thus, this research is essential to know the world about Dalit’s contribution to art creativity. This article concludes that oral traditional forms have their own representation style, and their aim is to express Dalits’ pain, injustice and struggle through traditional and modern forms of untouchability.