Oral Tablets Research Articles

Efficacy of Melatonin as an Adjunctive Therapy in Hospitalized Patients with Mild to Moderate COVID-19: A Randomized, Double-blind Clinical Trial

Background: Melatonin has proven antioxidant and anti-inflammatory properties that may address the pathophysiology of coronavirus disease 2019 (COVID-19). Therefore, the current study was conducted to evaluate the safety and efficacy of melatonin in COVID-19. Methods: In this single-center, randomized, double-blind, placebo-controlled clinical trial, 96 adults hospitalized with mild to moderate COVID-19 were recruited. The participants were allocated into the melatonin and the placebo groups, randomly (1:1 ratio). Results: The primary outcomes were a reduction in the length of hospital stay, the rate of ICU admissions, intubation/mechanical ventilation, and mortalities within 14 days of starting the treatment compared to the placebo group. After two weeks of follow-up, the blood oxygen saturation and the respiratory rate significantly improved in the melatonin group. C-reactive protein, erythrocyte sedimentation rate, lactate dehydrogenase, creatine phosphokinase, Ferritin, and D-dimer levels were significantly decreased in the melatonin group. Conversely, these markers were considerably increased in the placebo group. These serum marker levels also showed a significant difference in between- group comparison. The comparison of clinical endpoints between the two groups showed no significant difference. Conclusion: This clinical trial study indicated that the combination of oral melatonin tablets and standard treatment could substantially improve blood oxygen saturation and inflammatory factors in mild to moderate hospitalized COVID-19 patients.

Population Pharmacokinetic Modeling of Posaconazole in Japanese Patients Receiving Fungal Prophylaxis.

Posaconazole is a vital drug to treat and prevent invasive fungal infections. Several factors, such as sex, body weight, total serum proteins, dietary intake, and severe mucositis, affect posaconazole pharmacokinetics (PKs). However, the relevance of other factors that affect the PKs of posaconazole in hematopoietic stem cell transplantation (HSCT) is unknown. This study explored factors influencing the PKs of posaconazole in HSCT recipients and nontransplant patients with hematological diseases. The authors conducted a single-institution, retrospective study. Forty-two Japanese inpatients receiving oral posaconazole tablets as prophylaxis for fungal infections were enrolled in this study. A one-compartment model with first-order absorption was used as the structural pharmacokinetic model. A population PK (PopPK) analysis was performed using a nonlinear mixed-effects modeling program, using a first-order conditional estimation method with interactions. Perl-speaks-NONMEM and R were used to evaluate the goodness of fit and visualize the output. In 29% of the enrolled patients, the serum concentration of posaconazole was <0.5 mcg/mL, considered the effective range. PopPK analysis revealed that the patient had undergone HSCT within 1 year, diarrhea occurred more than 5 times a day, and aspartate aminotransferase were covariates that influenced apparent clearance (CL/F). The CL/F of posaconazole was 1.43-fold higher after HSCT and 1.26-fold higher during diarrhea. PopPK analysis revealed that HSCT, diarrhea, and aspartate aminotransferase were factors associated with the CL/F of posaconazole. The trough concentration of posaconazole may be below the therapeutic range in a few patients with diarrhea and/or after HSCT. As invasive fungal infections in patients with hematologic diseases can be life-threatening, therapeutic drug monitoring of posaconazole is strongly recommended, and patients should be carefully monitored.

A Green Approach to Synthesize Ondansetron Oral Mucoadhesive Tablets by Using Natural Polymers and in vitro Characterization

A Green Approach to Synthesize Ondansetron Oral Mucoadhesive Tablets by Using Natural Polymers and in vitro Characterization

Patient-Controlled Subcutaneous Analgesia with Hydromorphone versus Oral Oxycontin for Opioid Titration of Cancer Pain: A Prospective Multicenter Randomized Trial.

Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain. Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5-11.5] hours vs.16.0 [95% CI:11.5-22.5] hours; p<0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0-3.5) than in the oxycontin group.(3.0; 2.5-4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5-3.0) vs 4.5;3.0-6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32). Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p<0.001), without significantly increasing adverse events (p=0.32).

Clinical Benefits, efficacy and tolerability of slowly titrated vortioxetine oral drops solution

Introduction Vortioxetine is mainly prescribed as oral tablets, usually starting at 5-10 mg per day, and is well tolerated by most patients. However, some patients may experience side effects, the most common of which is nausea, which occurs in 20.9-31.2% of people treated with doses of 5-20 mg/day (Baldwin et al, J Psychopharmacol. 2016;30:242-52). In some countries, vortioxetine is also available as an oral solution (1 drop = 1 mg), which allows a very slow titration schedule that may improve tolerability.Objectives To evaluate whether vortioxetine oral drop solution, started with 1-2 drops (1-2 mg per day) and increased by 1-2 drops per day to 10-20 drops (10-20 mg), is associated with better tolerability and a lower risk of nausea than that observed with oral tablets started with 5-10 mg per day, while maintaining efficacy. To provide pilot data for the design of a multicentre, prospective study.MethodsRetrospective, single-centre, observational study. Participants were 58 consecutive patients (mean age 45 + 17 years, 55.2% female) treated with vortioxetine for a depressive episode. Vortioxetine was initiated and titrated up to 1 drop (1 mg) per day in 58.6% of subjects, and initiated and titrated up to 2 drops in 41.4% of subjects. Tolerability was assessed at all visits. CGI and MADRAS scores were recorded at the following time points: T0-baseline, T1=week 1, T2=week 2, T3=week 4, T4=week 8). Comparisons were made using repeated measures ANOVA with Bonferroni correction.ResultsNausea was reported by 8 subjects (13.8%) at T1, 4 subjects (6.9%) at T2, 1 subject at T3 (1.7%) and none at T4. Other adverse reactions (mainly dizziness, pruritus/itching, vomiting, diarrhoea, and xerostomia) were reported by a total of 6 subjects (10.3%) at T1, none at T2 and T3, and 1 subject (1.7%) at T4. The maximum dose administered was 20 mg in 75.9% of patients. No patients discontinued vortioxetine due to adverse events, but vortioxetine was discontinued prior to T4 (8 weeks of treatment) in 2 subjects due to lack of efficacy. The mean CGI at baseline was 4.3 ±0.8. The mean value decreased to 3.9±0.7 at week 1 and to 3.4±0.6, 2.7±0.6, 1.9±0.5 at weeks 2, 4 and 8, respectively. All differences were statistically significant (p&lt;0.001) compared to baseline. Also from week 2, all scores were statistically significant compared to all previous assessments. The total MADRS score decreased from 28.3±4.6 at baseline to 24.9±4.2, 20.9±4, 16.3±3.6 and 10.9±3 at weeks 2, 4 and 8, respectively. A significant decrease in MADRS total score was observed at each time point (p&lt;0.001) compared to baseline and previous assessments.ConclusionsSlow titration with vortioxetine oral drop solution was associated with a very low percentage of patients reporting side effects in general, and nausea in particular, and with a relatively rapid improvement in depressive symptoms.Disclosure of InterestNone Declared

12 Time to Sustained Recovery between Oral Tablet and Inhaler Placebos in the ACTIV-6 Platform Clinical Trial

OBJECTIVES/GOALS: Platform trials gain efficiency by sharing placebo controls among different study arms. However, the varying routes of administration make it unclear whether participants exposed to different placebos have similar outcomes. As such, we seek to compare outcomes between participants receiving tablet and inhaler placebos in the ACTIV-6 trial. METHODS/STUDY POPULATION: ACTIV-6 is a large, decentralized platform trial exploring repurposed drugs for the treatment of adults with mild to moderate COVID-19. Enrolled participants were randomly assigned to a study arm vs. placebo and then mailed the study drug. They were monitored until symptom resolution or Day 28. Here, we compare outcomes for control participants contributing to the fluticasone furoate study arm, in which 251 were assigned to a tablet placebo and 370 an inhaler placebo. Time to sustained recovery and time to resolution of individual symptoms are compared between groups using Kaplan-Meier curves and unadjusted log-rank tests. A step-down procedure is applied to control the false discovery rate. RESULTS/ANTICIPATED RESULTS: Control participants assigned to tablet placebos had shorter time to sustained recovery (adjusted hazard ratio (HR) 1.34 (95% CI 1.11, 1.62)). When examining each of the eleven individually reported symptoms on study Day 14, nasal symptoms (adjusted odds ratio (OR) 0.44 (0.27, 0.72), p&lt;0.01), dyspnea (OR 0.44 (0.22, 0.87), p = 0.02), and cough (OR 0.54 (0.35, 0.83), p&lt;0.01) were identified as symptoms in which the tablet-placebo group performed notably better than those who received inhaler-placebos. In the follow-up, longitudinal analysis, we anticipate similar results. DISCUSSION/SIGNIFICANCE: Among ACTIV-6 control participants, those receiving a tablet placebo had a significantly shorter time to sustained recovery than those receiving an inhaler placebo. Platform trials using shared controls should consider efficiency in the context of the additional variability when sharing controls with a different route of administration.

Schizophyllum Commune- A Rare Cause of Fungal Keratitis- Case Report and Review of Literature

Abstract We present a 57-year-old male patient with keratitis, he was initially started on topical 0.5% moxifloxacin eye drops, but his symptoms did not resolve and infiltrate continued to increase. Corneal scrapings and microbiological reports suggested the diagnosis of the fungus, Schizophyllum commune, the patient was then switched to topical 5% natamycin eye drops hourly for 1 week followed by eight times per day for 2 weeks and oral tablet fluconazole 200 mg twice daily, following which the infiltrate was reduced, hypopyon resolved and visual acuity improved after 2 weeks of treatment.

Bio-analytical Estimation of Metformin Co-administered with Antidiabetic and Antihyperlipidemic Herbal Preparations by LCMS

The antidiabetic and antihyperlipidemic herbal preparations were developed in liquid and oral tablet dosage form as Saptarangi Plus Kadha (SK) and Saptarangi Tablet (ST). Streptozotocin (STZ) (45mg/kg) was injected by single intraperitoneal (i.p.) injection and diabetes was induced in Wistar rats of group II to group VII. Metformin (100mg/kg, p.o.) was co-administered orally to group IV to VII with SK and ST as a reference standard drug. There is a need of bio-analytical study and standardization of herbal preparation which is required to get approval of the regulatory agencies for the commercialization. The estimation of metformin was carried in the presence of other herbal phytoconstituents by LCMS/MS. The samples of all the groups were centrifuged and vortexed. The samples were prepared in ACN: 0.1% formic acid (70:30) and LCMS method was developed and validated. The metformin was estimated in presence of active phytoconstituents of SK and ST. SK and ST contains Salacinol and folia salaciosides E1 which was detected by LCMS at m/z 333.42 and m/z 504.63 respectively. There has been an honest effort to create and validate LCMS method for the detection of metformin in presence of phytoconstituents of SK and ST in serum.

In-vivo and Histological Studies of Matrix-based Artemether-Lumefantrine Oral Tablets Derived from Cissus populnea Gum

In-vivo and Histological Studies of Matrix-based Artemether-Lumefantrine Oral Tablets Derived from Cissus populnea Gum

Tableting behavior of freeze and spray-dried excipients in pharmaceutical formulations

Most of biopharmaceuticals, in their liquid form, are prone to instabilities during storage. In order to improve their stability, lyophilization is the most commonly used drying technique in the pharmaceutical industry. In addition, certain applications of biopharmaceutical products can be considered by oral administration and tablets are the most frequent solid pharmaceutical dosage form used for oral route. Thus, the tableting properties of freeze-dried products used as cryo and lyoprotectant could be a key element for future pharmaceutical developments and applications. In this study, we investigated the properties that might play a particular role in the specific compaction behavior of freeze-dried excipients. The tableting properties of freeze-dried trehalose, lactose and mannitol were investigated and compared to other forms of these excipients (spray-dried, commercial crystalline and commercial crystalline milled powders). The obtained results showed a specific behavior in terms of compressibility, tabletability and brittleness for the amorphous powders obtained after freeze-drying. The comparison with the other powders showed that this specific tableting behavior is linked to both the specific texture and the physical state (amorphization) of these freeze-dried powders.

Is Diclofenac Transbuccal Mucoadhesive Patch Superior to Oral Diclofenac for the Management of Postoperative Sequelae After Third Molar Surgery?

Pain, swelling, and trismus are the most common sequalae following the surgical removal of mandibular third molars. They pose significant challenges for clinicians, prompting the exploration of efficacious management approaches. The purpose of this study was to assess the efficacy of transbuccal mucoadhesive patch of diclofenac sodium versus an oral tablet in controlling the aforesaid sequelae. A prospective split-mouth, single-blinded study was conducted in the Department of Oral and Maxillofacial Surgery at AMC Dental College and Hospital, Ahmedabad. The study sample included patients of either sex, aged 18 to 45years, requiring surgical removal of bilaterally symmetrical mandibular third molars under local anesthesia. Patients who had consumed analgesics within 24hours prior to the procedure were excluded. The primary predictor variable was the route of administration of nonsteroidal anti-inflammatory drug. The study group received transbuccal mucoadhesive patches containing 20mg diclofenac sodium, whereas the control group received oral tablets of 50mg. Postoperative pain, measured with visual analog scale, was the primary outcome variable, whereas swelling, mouth opening, onset of analgesic effect, and adverse events were assessed as secondary outcome variables. Two categories of covariates were considered. First, demographic: age and gender. Second, perioperative: pattern of impaction. Intergroup comparison was made using a paired sample t-test and an independent sample t-test, while intragroup differences were assessed with a one-way ANOVA and a paired t-test. P value ≤ .05 was considered statistically significant. Out of 146 patients screened initially, the final study sample included 37 subjects with a mean age of 26.08±5.09years (21 (56.75%) males and 16 (43.25%) females). The study group exhibited a significantly lower postoperative pain score compared to the control group on days 0, 1, 2, and 3 postoperatively (P≤.05). No statistically significant difference was observed in reduction of facial swelling and improvement in mouth opening on 1st, 2nd, and 3rd days postoperatively between both the groups (P≥.05). The mean onset of analgesia was statistically significant in the study group (19.96±5.40minutes) compared to the control group (52.56±6.33minutes) (P<.001). Transbuccal mucoadhesive patch of diclofenac sodium offers effective pain control with quicker analgesia and fewer side effects compared to an oral tablet.

Fabrication, optimization, and evaluation of lyophilized lacidipine-loaded fatty-based nanovesicles as orally fast disintegrating sponge delivery system

Lacidipine (LCD) is a potent antihypertensive agent. Fatty-based nanovesicles (FNVs) were designed to improve LCD low solubility and bioavailability. LCD-FNVs were formulated according to different proportions of cetyl alcohol, cremophor®RH40, and oleic acid adopting Box-Behnken Design. The optimized LCD-FNVs, composed of cetyl alcohol 48.4 mg, cremophor®RH40 120 mg, and oleic acid 40 mg, showed minimum vesicle size (124.8 nm), maximum entrapment efficiency % (91.04 %) and zeta potential (-36.3 mV). The optimized FNVs were then used to formulate the lyophilized orally fast-disintegrating sponge (LY-OFDS). The LY-OFDS had a very short disintegration time (58 sec), remarkably high % drug release (100 % after 15 mins), and increased the drug transbuccal permeation by over 9.5-fold compared to the drug suspension. In-vivo evaluation of antihypertensive activity in rats showed that the LY-OFDS reduced blood pressure immediately after 5 min and reached normal blood pressure 4.5-fold faster than the marketed oral tablets. In the In-vivo pharmacokinetic study in rabbits, the LY-OFDS showed 4.7-fold higher bioavailability compared with the marketed oral tablet. In conclusion, the LY-OFDS loaded with LCD-FNVs is a safe, and non-invasive approach that can deliver LCD effectively to the blood circulation via the buccal mucosa giving superior immediate capabilities of lowering high blood pressure and increasing the drug bioavailability.

Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole.

Posaconazole is a pharmacotherapeutic pillar for prophylaxis and treatment of invasive fungal diseases. Dose individualization is of utmost importance as achieving adequate antifungal exposure is associated with improved outcome. This study aimed to select and evaluate a model-informed precision dosing strategy for posaconazole. Available population pharmacokinetic models for posaconazole administered as a solid oral tablet were extracted from the literature and evaluated using data from a previously published prospective study combined with data collected during routine clinical practice. External evaluation and selection of the most accurate and precise model was based on graphical goodness-of-fit and predictive performance. Measures for bias and imprecision included mean percentage error (MPE) and normalized relative root mean squared error (NRMSE), respectively. Subsequently, the best-performing model was evaluated for its a posteriori fit-for-purpose and its suitability in a limited sampling strategy. Seven posaconazole models were evaluated using 764 posaconazole plasma concentrations from 143 patients. Multiple models showed adequate predictive performance illustrated by acceptable goodness-of-fit and MPE and NRMSE below ±10% and ±25%, respectively. In the fit-for-purpose analysis, the selected model showed adequate a posteriori predictive performance. Bias and imprecision were lowest in the presence of two prior measurements. Additionally, this model showed to be useful in a limited sampling strategy as it adequately predicted total posaconazole exposure from one (non-)trough concentration. We validated an MIPD strategy for posaconazole for its fit-for-purpose. Thereby, this study is an important first step towards MIPD-supported posaconazole dosage optimization with the goal to improve antifungal treatment in clinical practice.

Depression Among Pregnant and Breastfeeding Persons Participating in Two Randomized Trials of the Dapivirine Vaginal Ring and Oral Pre-Exposure Prophylaxis (PrEP) in Malawi, South Africa, Uganda, and Zimbabwe.

Depression is associated with lower adherence to oral pre-exposure prophylaxis (PrEP) to prevent HIV, but data are not currently available on how depression may affect use of other HIV prevention methods including the dapivirine vaginal ring (DVR). We conducted a mixed methods study using data from the Microbicide Trials Network (MTN) 042/DELIVER (n = 558) and MTN-043/B-PROTECTED (n = 197) studies to describe the prevalence of depressive symptoms and explore how depressive symptoms may have influenced attitudes about use of the monthly DVR and once-daily oral PrEP tablet among pregnant and breastfeeding persons, respectively, in Malawi, South Africa, Uganda, and Zimbabwe. Eleven participants had high Edinburgh Postnatal Depression scores ≥ 10 in MTN-042/DELIVER (2%) and four participants (2%) in MTN-043/B-PROTECTED. In interviews with 9 participants who had high scores (6 DVR, 3 oral PrEP), those with depressive symptoms described overlapping stressors which were magnified by job loss and economic instability during the COVID-19 pandemic, and by experiences of pregnancy/postpartum. These participants experienced a lack of support from partners or family members, and conflict with partners related to trust, and infidelity. While we did not find evidence of a change in product adherence, there was a strong sense of commitment and motivation to use the study products for protection from HIV for participants themselves and their baby. Although lack of social support is usually an obstacle to adherence, in this study, the participants' lives and relationships seemed to have reinforced the need for HIV prevention and motivated women to protect themselves and their babies from HIV.

Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

Thymopeptide Enteric-Coated Tablets Combined with Compound Kuwei Huoxue Formula in the Treatment of Oral Lichen Planus

The aim of this study was to explore the clinical efficacy and safety of the combination of thymopeptide enteric-coated tablets and Compound Kuwei Huoxue Formula in the treatment of oral lichen planus (OLP). Using a random number table, the patients were divided into a study group and a control group after registration and enrollment. There was no significant difference in the general data comparison between the two groups (P &gt; 0.05). After treatment, the number of cured patients in the study group was higher than that in the control group, and the number of ineffective cases was lower than that in the control group. The total cure rate in the study group was higher than that in the control group (P &lt; 0.05). The levels of inflammatory factors interleukin-4, interleukin-6, and interferon-γ in the study group. Based on the practical clinical considerations, the treatment regimen of oral immunomodulator-thymopeptide enteric-coated tablets combined with Compound Kuwei Huoxue Formula emphasizes enhancing the immune function of the body and adopting the principle of clearing heat and detoxification in traditional Chinese medicine to achieve the goal of treating the root cause. This comprehensive treatment approach has achieved good clinical efficacy, providing new ideas and methods for the treatment of OLP that are worth promoting.

Comparative evaluation of physical and chemical enhancement techniques for transdermal delivery of linagliptin

Linagliptin is a dipeptidyl peptidase-4 inhibitor used for the management of type-2 diabetes. US FDA-approved products are available exclusively as oral tablets. The inherent drawbacks of the oral administration route necessitate exploring delivery strategies via other routes. In this study, we investigated the feasibility of transdermal administration of linagliptin through various approaches. We compared chemical penetration enhancers (oleic acid, oleyl alcohol, and isopropyl myristate) and physical enhancement techniques (iontophoresis, sonophoresis, microneedles, laser, and microdermabrasion) to understand their potential to improve transdermal delivery of linagliptin. To our knowledge, this is the first reported comparison of chemical and physical enhancement techniques for the transdermal delivery of a moderately lipophilic molecule. All physical enhancement techniques caused a significant reduction in the transepithelial electrical resistance of the skin samples. Disruption of the skin’s structure post-treatment with physical enhancement techniques was further confirmed using characterization techniques such as dye binding, histology, and confocal microscopy. In vitro permeation testing (IVPT) demonstrated that the passive delivery of linagliptin across the skin was < 5 µg/sq.cm. Two penetration enhancers - oleic acid (93.39 ± 8.34 µg/sq.cm.) and oleyl alcohol (424.73 ± 42.86 µg/sq.cm.), and three physical techniques - iontophoresis (53.05 ± 0.79 µg/sq.cm.), sonophoresis (141.13 ± 34.22 µg/sq.cm.), and laser (555.11 ± 78.97 µg/sq.cm.) exceeded the desired target delivery for therapeutic effect. This study established that linagliptin is an excellent candidate for transdermal delivery and thoroughly compared chemical penetration and physical transdermal delivery strategies.

Perceptions and experiences of intravenous iron treatment for anaemia in pregnancy in Malawi: a formative qualitative study

Background The study objective was to explore opinions, identify experiences, and describe perspectives on the acceptability of intravenous (IV) iron to treat anaemia in pregnancy and identify potential barriers and facilitators of introducing IV iron in the Malawian healthcare system. Methods We conducted 15 in-depth interviews and two focus group discussions with pregnant women, and seven in-depth interviews with health workers at a community-based health centre in Blantyre and a tertiary hospital in Zomba. Results Most women who used IV iron treatment during the second trimester of pregnancy reported feeling better and stronger after receiving the intervention. Women perceived that IV iron treatment worked faster than oral iron tablets and increased their haemoglobin count. However, cultural beliefs that IV iron treatment will cause miscarriage and the perception that study procedures involved Satanism and vampirism practices were barriers to acceptability. Health workers found IV iron treatment easy to administer because it is a single-dose treatment, simultaneously reducing the burden for pregnant women taking daily oral iron tablets. However, health workers expressed concerns about the costs and the need to train health workers before the large-scale implementation and integration of IV iron treatment into Malawi’s routine care. Conclusions Despite the perceived concerns and challenges experienced in participating in the first IV iron infusion trial in Malawi, participants’ reflections suggest that IV iron infusion is acceptable for treating iron-deficiency anaemia in pregnancy. Participant advocate groups can offer a peer-to-peer education approach to sensitize and engage community members on the benefits of treatment and dispel concerns when the country contemplates integrating IV iron infusion for treating anaemia in pregnancy in Malawi.

Fabrication of a Controlled-Release Core-Shell Floating Tablet of Ketamine Hydrochloride Using a 3D Printing Technique for Management of Refractory Depressions and Chronic Pain.

In this study, a novel floating, controlled-release and core-shell oral tablet of ketamine hydrochloride (HCl) was produced using a dual extrusion by 3D printing method. A mixture of Soluplus® and Eudragit® RS-PO was extruded by a hot-melt extrusion (HME) nozzle at 150-160 °C to fabricate the tablet shell, while a second nozzle known as a pressure-assisted syringe (PAS) extruded the etamine HCl in carboxymethyl cellulose gel at room temperature (25 °C) inside the shell. The resulting tablets were optimized based on the United States pharmacopeia standards (USP) for solid dosage forms. Moreover, the tablet was characterized using Fourier-transform infrared (FTIR) spectrum, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and buoyancy techniques. The results showed a desired dissolution profile for a 100% infill optimized tablet with total drug release (100%) during 12 h. Weight variation and content uniformity of the tablets achieved the USP requirements. SEM micrographs showed a smooth surface with acceptable layer diameters. According to the FTIR analysis, no interference was detected among peaks. Based on DSC analysis, the crystallinity of ketamine HCl did not change during melt extrusion. In conclusion, the floating controlled-release 3D-printed tablet of ketamine HCl can be a promising candidate for management of refractory depressions and chronic pain. Additionally, the additive manufacturing method enables the production of patient-tailored dosage with tunable-release kinetics for personalized medicine in point-of care setting.

DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF LORATADINE SUSTAINED RELEASED BUCCAL FILM: IN VITRO AND IN VIVO STUDY IN BEAGLE DOGS

Objective: The aim of this work was to develop and evaluate bucco-adhesive films of Loratadine (LTD) for sustained release use. Methods: Design of twelve different sustained released buccal film formulas using Carbopol, pectin, sodium alginate, glycerol, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), Gelatin, Hydroxyethyl cellulose (HEC), and Hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Films were evaluated for physicochemical properties, thickness, swelling, moisture content, drug content, in vitro dissolution. The pharmacokinetic parameters of optimal formula were evaluated in beagle dogs. Results: The selected film formula (F6) showed accepted content and muco-adhesion properties. The in vitro release study showed prolonged release of drug from films over 10 h in optimal formulation. The bioavailability studies performed using beagle dogs model showed that there was 113.45% increase in the AUC0-24 of selected film compared with oral market tablets. Conclusion: Bucco-adhesive films is a promising dosage form for improving the bioavailability of loratadine.