Oral Tablets Research Articles

Formulation Development and Evaluation of Ticagrelor Oral Dispersible Tablets by Using Co-processed Superdisintegrants

Ticagrelor is a contemporary anti-platelet drug that inhibits the aggregation of platelets by blocking the adenosine phosphate (ADP) receptors of the subtype P2Y12; generally utilized in patients who have a previous history of myocardial infarction or with acute coronary syndrome to prevent occurring of myocardial infarction, cardiovascular death and stroke in future. This study focuses on the development of formulation development & assessment of an oral dispersible tablet of ticagrelor, a Biopharmaceutical Classification System (BCS) class 4 drug, by using the co-processed superdisintegrants to enhance drug dissolution and bioavailability. Wet granules with different concentrations of co-processed superdisintegrants developed the tablets. This study includes seven formulations that were formulated using the different selected excipients. The various batches were assessed for physical characteristics, disintegration, dissolution studies, hardness and friability. In-vitro dissolution investigations were conducted for formulations. S1 to S7 at time points 5, 15 and 30 minutes. According to the results of the formulation S7 was discovered to be the optimum formulation, as shown 102.89% drug release at 5 minutes and a disintegration time of 16 seconds. Thus, it appears that S7 is the most suitable formulation of ticagrelor oral dispersible tablet in order for enhanced bioavailability.

Microporation-Mediated Transdermal Delivery of In Situ Gel Incorporating Etodolac-Loaded PLGA Nanoparticles for Management of Rheumatoid Arthritis.

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and -6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and -23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).

Emerging Technologies in Endocrine Drug Delivery: Innovations for Improved Patient Care.

Recent advancements in drug delivery systems for endocrine disorders have significantly improved patient outcomes by addressing the limitations of traditional methods such as oral tablets and injections. These innovations include non-invasive alternatives like inhaled insulin, which provides rapid absorption and better patient compliance, and robotic pills that deliver drugs directly to specific gastrointestinal sites, enhancing absorption and reducing side effects. Wearable artificial pancreas systems have revolutionized diabetes management by integrating continuous glucose monitoring with insulin pumps to automate blood glucose control. These systems demonstrate superior glycemic control and reduce hypoglycemic events. Additionally, smart insulin pens enhance diabetes care through dose tracking and real-time data sharing, improving accuracy and adherence. Microneedle patches offer a minimally invasive method for transdermal drug delivery, effectively administering hormones and therapeutic peptides without the pain and inconvenience of injections. These patches dissolve after use, eliminating biohazardous waste. Implantable devices provide long-term, controlled release of medications, significantly improving adherence and glycemic control of patients with diabetes. Hydrogels also offer new drug delivery options. This review examines these technologies' clinical efficacy, safety, advantages, and limitations, highlighting their potential to transform endocrine disorder management. Integrating advanced delivery systems marks a significant step towards personalized medicine, tailoring treatments to individual patient needs for better health outcomes.

Understanding medication recycling practices in Canadian hospitals.

Medication recycling within hospitals has proven financial and possible environmental benefits according to local evaluations done in British Columbia. Despite this, the extent of medication recycling in Canadian hospitals remains unclear in the literature. To determine if Canadian hospitals recycle medications, provide an estimate of how much medication is recycled by dosage form, and identify medication recycling barriers through the distribution of a cross-sectional survey. A nine-question survey was distributed to 171 hospital pharmacy departments across Canada that consented to complete the survey. The survey identified whether sites recycled unused medications, an estimate of how much is recycled based on dosage form, and barriers to recycling. Of 62 respondents, the majority indicated they do have medication recycling procedures; however, the frequency of recycling is suboptimal (30-50% of medications are not recycled), and not all medication types are always recycled. Individually packaged oral tablets were most often recycled, and oral liquid medications were least often recycled. Many multi-dose medications were not tamper-proofed. Most respondents selected "sanitization/infection control" and "resource constraint" as reasons for not recycling all medications. Among respondents, the proportion and type of unused medicines that are recycled varied. For sites that did not respond, this might suggest that medication recycling is not a priority. This could represent a missed opportunity to standardize practices and increase medication recycling in hospitals, both of which could represent a meaningful step towards responsible use of medications and reduction of negative impacts on human health and the environment.

Effects of Functional Biomaterials on the Attributes of Orally Disintegrating Tablets Loaded with Furosemide Nanoparticles: In Vitro and In Vivo Evaluations.

Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the Biopharmaceutics Classification System. It is practically insoluble in water. This study aimed to optimize and formulate porous orally disintegrating tablets (ODTs) prepared by sublimation and loaded with FUR nanoparticles prepared by using a planetary ball mill. Different functional biomaterials called stabilizers were used to stabilize the nanoparticle formula. Pluronic F-127 was the optimum stabilizer in terms of particle size (354.07 ± 6.44), zeta potential (-25.3 ± 5.65), and dissolution efficiency (56.34%). The impact of the stabilizer concentration was studied as well, and a concentration of 3% showed the smallest particle size (354.07 ± 6.44), best zeta potential value (-25.3 ± 5.65), and percentage of dissolution rate (56.34%). A FUR-loaded nanoparticle formula was successfully prepared. The nanoparticle formula was stabilized by using 3% pluronic F-127, and 3% was chosen for further study of the incorporation into oral disintegration tablets prepared by the sublimation technique. The impact of the matrix sublimating agent and superdisintegrant on the ODTs' attributes (in vitro disintegration, wetting time, and in vitro dissolution efficiency) was studied using 32 full factorial designs. In vivo, the diuretic activity was tested for the optimized FUR ODTs by calculating the Lipschitz value using rats as an animal model. The stability of the ODTs loaded with FUR nanoparticles was assessed under accelerated conditions for 6 months. Finally, the ODT formula loaded with FUR NPs showed a rapid onset of action that was significantly faster than untreated drugs. Nanonization and ODT formulation enhances the dissolution rate and bioavailability of FUR. Many factors can be controlled to achieve optimization results, including the formulation and process parameters.

Treatment Preferences for Acute Allergic Reactions: A Discrete Choice Experiment

Background: Timely treatment of acute allergic reactions (AARs) is important to minimize reaction severity. Corticosteroid tablets dissolved in water are commonly used in mainstay treatment. A new oral film that dissolves on the tongue provides a faster and less cumbersome alternative to tablets for corticosteroid administration during AARs. This study evaluated patients’ preferences for attributes related to administration mode of corticosteroids in AARs. Methods: A web-based survey was sent to a sample from the adult Swedish population (≥18 years) with experience of corticosteroid treatment for AAR. We assessed the willingness to pay (WTP) for attributes related to corticosteroid treatment by applying a discrete choice experiment (DCE) approach. DCE attributes were administration mode, time to symptom relief, and price. The WTP for each attribute was derived using the attribute’s coefficient in a logistic regression analysis. We specified a forced choice (FC) and an unforced choice (UC) model. In the FC model, the respondents chose between 2 hypothetical treatments and in the UC model, between any of 2 hypothetical treatments and their current treatment. Results: The final study population included 348 subjects, of which 80% were women. All the evaluated DCE attributes were significant predictors for the treatment choice (p<.001). In the FC model, the incremental WTP for an oral film compared with tablets was 409 Swedish kronor (SEK [≈€36.7]), with no other factors considered. In the UC model, the incremental WTP for the oral film compared with tablets was 574 SEK (≈€51.7). After considering the value of the respondents’ current treatment, the WTP for the oral film decreased to 336 SEK (≈€30.3). The total WTP was reduced by 17 SEK (≈€1.5) per minute of shorter time to symptom relief. Subgroup analyses showed that people with circulatory symptoms and experience of swallowing difficulties related to allergy medication had higher WTP for the oral film than the average respondent. Conclusion: The findings show a substantial economic benefit of the oral film vs tablets for patients with AARs in Sweden. This result remained also after compensation for the full value of the patients’ current treatment.

Treatment Preferences for Acute Allergic Reactions: A Discrete Choice Experiment

Background: Timely treatment of acute allergic reactions (AARs) is important to minimize reaction severity. Corticosteroid tablets dissolved in water are commonly used in mainstay treatment. A new oral film that dissolves on the tongue provides a faster and less cumbersome alternative to tablets for corticosteroid administration during AARs. This study evaluated patients’ preferences for attributes related to administration mode of corticosteroids in AARs. Methods: A web-based survey was sent to a sample from the adult Swedish population (≥18 years) with experience of corticosteroid treatment for AAR. We assessed the willingness to pay (WTP) for attributes related to corticosteroid treatment by applying a discrete choice experiment (DCE) approach. DCE attributes were administration mode, time to symptom relief, and price. The WTP for each attribute was derived using the attribute’s coefficient in a logistic regression analysis. We specified a forced choice (FC) and an unforced choice (UC) model. In the FC model, the respondents chose between 2 hypothetical treatments and in the UC model, between any of 2 hypothetical treatments and their current treatment. Results: The final study population included 348 subjects, of which 80% were women. All the evaluated DCE attributes were significant predictors for the treatment choice (p<.001). In the FC model, the incremental WTP for an oral film compared with tablets was 409 Swedish kronor (SEK [≈€36.7]), with no other factors considered. In the UC model, the incremental WTP for the oral film compared with tablets was 574 SEK (≈€51.7). After considering the value of the respondents’ current treatment, the WTP for the oral film decreased to 336 SEK (≈€30.3). The total WTP was reduced by 17 SEK (≈€1.5) per minute of shorter time to symptom relief. Subgroup analyses showed that people with circulatory symptoms and experience of swallowing difficulties related to allergy medication had higher WTP for the oral film than the average respondent. Conclusion: The findings show a substantial economic benefit of the oral film vs tablets for patients with AARs in Sweden. This result remained also after compensation for the full value of the patients’ current treatment.

P2X3 Receptor Antagonist Eliapixant in Phase I Clinical Trials: Safety and Inter-ethnic Comparison of Pharmacokinetics in Healthy Chinese and Japanese Participants.

Afferent neuronal hypersensitization via P2X3 receptor signaling has been implicated as a driver of several disorders, including refractory chronic cough, endometriosis, diabetic neuropathic pain, and overactive bladder. Eliapixant, a selective P2X3 receptor antagonist, has been in clinical development for all four disorders. This paper describes pharmacokinetic (PK) and safety data from two phase I studies of eliapixant in healthy Japanese and Chinese participants and compares those data within the two populations and with previous multiple dose data from Caucasian participants. Two separate phase I, single-center, randomized, placebo-controlled studies were conducted with healthy male participants. The Japanese study was single-blind and the Chinese study was double-blind. Eliapixant was administered as an oral amorphous solid dispersion immediate-release tablet in strengths of 25 mg, 75 mg, and 150 mg. PK characteristics after a single dose (SD) and at steady state (multiple dose [MD], twice daily), adverse events (AEs), and tolerability were evaluated. A post hoc comparison of PK characteristics after SD of eliapixant in Japanese and Chinese participants, and after MD of eliapixant in Japanese, Chinese, and Caucasian participants, was performed. Overall, 36/39 participants enrolled in the Japanese/Chinese studies, respectively (mean [standard deviation] age 25.4 [6.5] and 26.7 [5.0] years, respectively). After SD administration, maximum plasma concentration (Cmax) was higher among Japanese than Chinese participants in the 25 mg and 75 mg dose groups, but comparable in the 150 mg dose group. The area under the concentration-time curve (AUC) was comparable between Japanese and Chinese participants in the 25 mg and 75 mg dose groups, but lower among Japanese participants in the 150 mg group. Half-lives after SD and MD administration were also comparable in Japanese and Chinese participants. The post hoc analysis included 26 Japanese, 30 Chinese, and 50 Caucasian participants. Comparable exposure (Cmax,md and AUC[0-12]md) was observed after MD administration of eliapixant in Chinese and/or Japanese compared with Caucasian participants (geometric mean inter-ethnic ratios close to 1). The trough plasma concentration after eliapixant 150 mg MD, which was assumed to be relevant to eliapixant efficacy, was comparable across all ethnicity groups. Most AEs reported in the Japanese (eliapixant 75 mg SD, n = 2; eliapixant 150 mg MD, n = 2) and Chinese participants (eliapixant 25 mg SD, n = 7; eliapixant 75 mg SD, n = 6; eliapixant 150 mg SD, n = 7; eliapixant 150 mg MD, n = 9; placebo SD, n = 5; placebo MD, n = 1) were of mild intensity. Higher incidences of AEs in the Chinese population were likely due to differing standards of AE reporting between investigators. Eliapixant was well tolerated by Japanese and Chinese participants. The inter-ethnic evaluation demonstrated similar PK characteristics across Japanese, Chinese, and Caucasian participants. ClinicalTrials.gov identifier numbers: NCT04265781 and NCT04802343.

Staged Surgical Treatment of the Giant Pituitary Neuroendocrine Tumors

To investigate the long-term clinical outcomes of staged surgical resection in giant Pituitary Neuroendocrine Tumors(pitNET).Method We performed a retrospective analysis of the clinical data of 16 patients who underwent surgery. The patients were diagnosed and underwent surgery at the Department of Neurosurgery of Shiyan Taihe Hospital from January 2013 to March 2021. Among the cases, 12 patients underwent primarily transsphenoidal surgery followed by secondary transcranial surgery, while 4 patients underwent primarily transsphenoidal surgery followed by secondary transsphenoidal surgery. Before the surgery, all patients underwent a pituitary MRI scan, pituitary hormone level examination, visual acuity, and visual field examination. A pituitary MRI was rechecked within 1 week after the operation. A tumor resection rate of 100% on MRI was considered as a total resection, between 90% to 100% as a subtotal resection, and lower than 90% as a partial resection. After the surgery, regular clinical visits and telephone or internet platform follow-ups were conducted. Outcome In our clinical investigation, after staged surgery 10 patients had a total resection, 5 had a subtotal resection, and 1 had a partial resection depending on the tumor size and invasion. The clinical outcomes showed that 1 case suffered from postoperative intracranial infection, 1 case had decreased visual acuity, and 6 cases experienced decreased pituitary function after surgery.Postoperative complications were cured after symptomatic treatment, except for 1 patient who experienced decreased vision and 1 patient sufferred hypopituitarism required long-term oral levothyroxine tablet treatment. No cases of intracranial hemorrhage or death were caused by intentionally staged resection surgery. Conclusion Staged surgery for giant pitNET is a safe and effective clinical surgery strategy.

Design, optimization and characterization of atorvastatin loaded chitosan-based polyelectrolyte complex nanoparticles based transdermal patch

AimAtorvastatin (ATO) loaded chitosan-based polyelectrolyte complex nanoparticles (PECN) incorporated transdermal patch was developed to enhance its skin permeability and bioavailability. MethodologyThe ATO loaded PECN were prepared by ionic gelation method and optimized by Box-Behnken design. The optimized batches were evaluated for physicochemical characteristics, in vitro, ex vivo, cell line and stability studies. The optimized ATO-PECN were incorporated into transdermal patches by solvent evaporation method and evaluated for their physicochemical properties, ex vivo skin permeation, in vivo pharmacokinetics and stability study. ResultsThe optimized batch of ATO-PECN had average size of 219.2 ± 5.98 nm with 82.68 ± 2.63 % entrapment and 25.41 ± 3.29 mV zeta potential. ATO-PECN showed sustained drug release and higher skin permeation. The cell line study showed that ATO-PECN increased the cell permeability of ATO as compared to ATO suspension. ATO-PECN loaded transdermal patch showed higher skin permeation. The in vivo pharmacokinetic study revealed that the ATO-PECN transdermal patch showed significant (p < 0.05) increase in pharmacokinetic parameters as compared to marketed oral tablet, confirming enhancement in bioavailability of ATO. ConclusionsThe results of the present work concluded that the ATO-PECN loaded transdermal patch is a promising novel drug delivery system for poorly bioavailable drugs.

Targeting replication stress in pancreatic cancer: A phase II trial investigating azenosertib in combination with gemcitabine in second-line advanced pancreatic cancer.

TPS4211 Background: A major unmet need in pancreatic cancer (PDAC) is molecularly targeted treatment options for patients who develop resistance to first-line platinum chemotherapy. While combined gemcitabine and nab-paclitaxel is commonly used after progression with first-line therapy, the efficacy in the second-line setting is fair, with recent phase clinical trial data demonstrating a median progression-free survival (PFS) of 2.7 months and a median overall survival of 6.6 months (1). In recent years, preclinical work has identified that replication stress is a potential PDAC vulnerability. The WEE1 kinase regulates the checkpoint governing the G2/M transition of the cell cycle to compensate for replication stress. The G2/M checkpoint is critically important in malignancies like PDAC where over 75% of tumors have p53 pathway deficits. Therapies that inhibit cancer cells’ ability to compensate for replication stress are particularly attractive in cancers that have genomic alterations that generate replication stress. It has been demonstrated that in vitro and in vivo PDAC models were exquisitely sensitive to WEE1 inhibition in combination with gemcitabine. Azenosertib (Zn-c3) is an orally available, highly selective, nanomolar inhibitor of the WEE1 kinase and when combined with gemcitabine in PDAC cell lines, synergistic cytotoxicity is observed. Methods: NCT06015659 is an ongoing phase II clinical trial with safety lead-in that is testing the azenosertib WEE1 inhibitor combined with gemcitabine in patients with advanced pancreatic cancer after progression or intolerance with FOLFIRINOX. Subjects are dosed once daily, days 1-5, 8-12, and 15-19 with azenosertib and receive gemcitabine 800 mg/m2 on days 1 and 8 of 21-day cycles. Up to 12 subjects are expected to enroll in the safety lead-in portion based on a typical 3 + 3 design. Once the recommended phase 2 dose is confirmed, we will use a Simon two-stage minimax design to evaluate efficacy where the null hypothesis is that the true 6-month PFS rate is ≤ 24% (unacceptable historical control data) and the alternative hypothesis is that the true 6-month PFS is ≥ 44%. Pretreatment and on-treatment tumor biopsies are incorporated into the trial to identify potential biomarkers of treatment response. Subjects must be able to swallow oral tablets and have measurable disease by RECIST v1.1; prior exposure to gemcitabine is not allowed. Enrollment began November 21, 2023, and is ongoing. 1. Huffman BM, Basu Mallick A, Horick NK, et al. JAMA Netw Open. 2023;6(1):e2249720. Clinical trial information: NCT06015659 .

Review of Oral Tablet

Abstract: Oral drug delivery is noninvasive, has a high rate of patient compliance, is easy to handle, and doesn't require any special sterile settings, it is the most popular method of administration. Nevertheless, a number of physical, biological, and pharmacological obstacles that certain medications must overcome in order to be absorbed into the systemic circulation reduce their therapeutic efficiency. The use of nanocarriers to deliver drugs orally has proven to be an effective solution to the aforementioned problems and is being explored as a potential replacement for oral medication administration. This chapter provides an overview of the latest developments in the use of nanocarriers for oral medication delivery in the treatment of different disorders. The chapter also describes how diverse nanocarrier designs and technologies improve therapeutic potential by overcoming physical, biological, and biochemical obstacles. it is easy to produce, has few sterility limitations, is less expensive, has flexible dosage form design, and has high patient compliance, oral drug delivery (ODD) is the most convenient and favored method of drug administration. However, low medication bioavailability—which is influenced by three crucial factors—is one of the difficulties associated with oral drug delivery. The other is solubility. Many mathematical models that predict the medication's rate of solubility and dissolution have been developed in order to achieve efficient drug absorption in vivo. Similarly, models that are noncellular and cellular determine permeability. Furthermore, the medication's behavior in the gastrointestinal tract (GIT) is influenced by physiological parameters, such as pH, microbial colonization, and enzymes, as well as intrinsic drug properties. A drug's dosage form is a method of getting it into a living organism. The medicine must be administered to the site of action at a rate and concentration that will maximize therapeutic benefit and minimize side effects in order to provide the intended result. Although the oral method is still commonly used, swallowing tablets and capsules can be a regular problem. As a result, numerous studies on cutting-edge drug delivery methods have been conducted. This review focuses on oral dispersible tablets, a novel approach to drug delivery systems that are currently more focused on formulation and set a new course that not only helped patients increase their level of therapy compliance.

The effectiveness of relugolix compared with leuprorelin for preoperative therapy before laparoscopic myomectomy in premenopausal women, diagnosed with uterine fibroids: protocol for a randomized controlled study (MyLacR study)

BackgroundThe oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss.MethodsEfficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants (n = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1–5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms—Quality of Life).DiscussionReal-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy.Trial registrationjRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp).

Long acting paliperidone injection in patient with bipolar affective disorder, current episode manic with psychotic symptoms

Bipolar Disorder is a chronic mental illness characterized by periods of mania, depression, and mixed episodes that often need lifelong medication. The first line of pharmacotherapy includes lithium, valproate, or second-generation antipsychotics. Paliperidone is a medication that works in the brain and is also known as a second-generation antipsychotic. Paliperidone is available as an oral extended-release tablet and a once-monthly extended-release suspension for intramuscular injection. Long-acting injectables (LAIs) are used to reduce the non-adherence of oral medication. Paliperidone is one of the LAI that could be used to treat manic, hypomanic, and mixed episodes in patients with bipolar disorder. Paliperidone LAI reduces the number of relapses, hospitalization, and length of stay. As reported in this case, a patient with a manic episode who received paliperidone LAI showed favourable results after a week-long observation with no signs of extrapyramidal symptoms.

Widespread form of Majocchi's granuloma in a kidney transplant recipient.

Kidney transplantation is the encouraged kidney replacement therapy due to providing more prolonged survival with a better quality of life. Unfortunately, kidney transplant recipients are susceptible to infections because of long-term utilization of immunosuppression. Despite dermatophyte infections are generally not life-threatening, the clinical significance has been recently enhanced by an increasing number of immunocompromised patients. We have presented a rare dermatophytosis course, Majocchi's granuloma, that spreads to all extremities during the early post-transplant period. A young kidney transplant recipient was exposed to intensive immunosuppression therapy due to acute rejection in the early period of post-transplantation. After four months, numerous nodular skin lesions were raised on various body parts. An invasive fungal infection was identified in the skin biopsy. Also, Trichophyton rubrum was isolated in the tissue cultures. Consequently, the patient was diagnosed with Majocchi's granuloma. An effectual treatment was attained with an oral terbinafine tablet. Majocchi's granuloma is a distinct form of dermatophytosis characterized by the spreading of infection into the dermis. In this unexpected case, we alerted physicians to opportunistic infections in the kidney transplant recipient.

Quantification of isoniazid in tablets for tuberculosis treatment by thin layer chromatography with smartphone image capture and ImageJ analysis

Isoniazid (INH) oral dosage tablets are an antibacterial medication commonly used to treat tuberculosis (TB). While this medication can be highly effective in managing and curing TB, manufacturing of poor-quality INH products can lead to the proliferation of drug resistant TB strains – particularly in low- and middle-income countries (LMICs). It is therefore imperative that reliable methods of quality screening of INH tablets are available for areas that have limited access to traditional testing resources. In this study, a thin layer chromatography (TLC) procedure for INH identification is validated in conjunction with smartphone image capture and open-source image analysis software to provide an alternative quantitative quality screening method for INH tablets, primarily intended for applications in LMICs. The method assessed two individual tablet formulations: 100 mg and 300 mg INH, each from different manufacturers. The modified TLC procedure used for the study was based on a validated high-performance thin layer chromatography method for the determination of rifampicin, INH, and pyrazinamide in a fixed dosage tablet. Quantitation was performed by visualizing and photographing TLC plates using a UV lamp, 3D-printed light box, and Apple iPhone SE 2nd Generation (2020) and Google Pixel 4a (5G) smartphones, and images were then analyzed using ImageJ Fiji software. The processed images’ pixel data were used to create a calibration curve from the INH standard spots to determine the concentration of an INH sample spot. Linearity, range, accuracy, repeatability and intermediate precision, specificity, and robustness were evaluated. The method was linear in the range of 0.150–0.450 mg mL−1, with coefficients of determination ≥0.98. The overall accuracy of the method was 99.2 % with an RSD of 2.4 % for image sets captured using the Apple iPhone, and 99.7 % with an RSD of 3.3 % for image sets captured using the Google Pixel. The pooled standard deviations for repeatability and intermediate precision were 2.27 % and 3.25 %, respectively, for the iPhone and 2.62 % and 3.74 %, respectively, for the Pixel. The method demonstrated sufficient specificity and robustness. The results of this method validation suggest that this procedure may provide a feasible alternative to traditional testing as a low-cost means of quality screening in LMICs.

Impact of ivermectin components on Anopheles dirus and Anopheles minimus mosquito survival

BackgroundIvermectin mass drug administration to humans or livestock is a potential vector control tool for malaria elimination. Racemic ivermectin is composed of two components, namely a major component (> 80%; ivermectin B1a), which has an ethyl group at C-26, and a minor component (< 20%; ivermectin B1b), which has a methyl group at C-26. There is no difference between the efficacy of ivermectin B1a and ivermectin B1b efficacy in nematodes, but only ivermectin B1b has been reported to be lethal to snails. The ratios of ivermectin B1a and B1b ratios in ivermectin formulations and tablets can vary between manufacturers and batches. The mosquito-lethal effects of ivermectin B1a and ivermectin B1b have never been assessed. As novel ivermectin formulations are being developed for malaria control, it is important that the mosquito-lethal effects of individual ivermectin B1a and ivermectin B1b compounds be evaluated.MethodsRacemic ivermectin, ivermectin B1a or ivermectin B1b, respectively, was mixed with human blood at various concentrations, blood-fed to Anopheles dirus sensu stricto and Anopheles minimus sensu stricto mosquitoes, and mortality was observed for 10 days. The ivermectin B1a and B1b ratios from commercially available racemic ivermectin and marketed tablets were assessed by liquid chromatography-mass spectrometry.ResultsThe results revealed that neither the lethal concentrations that kills 50% (LC50) nor 90% (LC90) of mosquitoes differed between racemic ivermectin, ivermectin B1a or ivermectin B1b for An. dirus or An. minimus, confirming that the individual ivermectin components have equal mosquito-lethal effects. The relative ratios of ivermectin B1a and B1b derived from sourced racemic ivermectin powder were 98.84% and 1.16%, respectively, and the relative ratios for ivermectin B1a and B1b derived from human oral ivermectin tablets were 98.55% and 1.45%, respectively.ConclusionsThe ratio of ivermectin B1a and B1b does not influence the Anopheles mosquito-lethal outcome, an ideal study result as the separation of ivermectin B1a and B1b components at scale is cost prohibitive. Thus, variations in the ratio of ivermectin B1a and B1b between batches and manufacturers, as well as potentially novel formulations for malaria control, should not influence ivermectin mosquito-lethal efficacy.Graphical abstract

A case report on use of ivermectin as nasal drop in a case of nasal myiasis

We describe a case of nasal myiasis due to in a 52-year-old Hindu priest with a previously known case of right sided hemiparesis with diabetes mellitus. Initial attempts to remove the fly larvae using manual extraction with a toothed forceps and normal saline irrigation were unsuccessful. On subsequent nasal irrigation after instillation of ivermectin tabs crushed in normal saline as nasal drops, the patient self-expulsed some larvae, and rest larvae were cleared on subsequent nasal suction and clearance. He also received a course of oral ivermectin. Here, we propose that the antiparasitic oral tablet ivermectin can be used in a nasal drop formulation for the aid of nasal myiasis.

New Hydrophilic Matrix Tablets for the Controlled Released of Chlorzoxazone.

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.

Formulation and Evaluation of Immediate-Release Oral Tablets Containing Magnesium Aluminum Silicate-Loaded Simvastatin

Background: Simvastatin (SIM) is a lipid-lowering agent to prevent disorders caused by clogged blood vessels. Because of its low solubility, it has low bioavailability. The adsorption technique is effective in improving drug solubility and dissolution rate. Objective: To use magnesium aluminum silicate (MAS) as an adsorbent in combination with Soluplus® as a hydrophilic polymer to formulate SIM as immediate-release tablets (IRTs). Methods: We used the solvent evaporation method to make MAS-loaded SIM in the presence of Soluplus®, making sure that the ratio of SIM to MAS to SOLU was 1:6:3. We then used this mixture to make IRTs. Using the direct compression method, we made all of the SIM-IRT formulas. We used diluents like Avicel®PH102, Avicel®PH101, and starch, as well as super disintegrants like Crospovidone (CP), Croscarmellose sodium (CCS), and sodium starch glycolate (SSG). We evaluated these formulas for their weight variation, hardness, friability, disintegration time, drug content, and dissolution profile. Results: We prepared the tablet formula (T5) using MAS-loaded SIM, Avicel®PH102 as a diluent, and CCS 3% as a super disintegrant. This formula showed the shortest disintegration time (0.61 min) and best drug release in phosphate buffer pH 7.0, releasing more than 80% of the drug within 30 minutes. Conclusion: Using suitable excipients, adsorption was an efficient method to enhance the solubility of SIM for preparation as IRTs.