Search Results (23)

Background/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-β-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug. Full article

This article reports the case of a patient with a gastric neoplasm and total gastrectomy, presenting with severe digestive intolerance, who developed peritoneal and pulmonary tuberculosis. Standard treatment could not be administered. Therefore, treatment was initiated with isoniazid and rifampicin suppositories, and intravenous levofloxacin and amikacin, with significant remission of the digestive symptomatology. Although treatment with rifampicin suppositories has demonstrated efficacy in tuberculosis, it is rarely used in practice. This case highlights the importance of individualizing tuberculosis treatment and demonstrates that rectal administration of isoniazid and rifampicin suppositories, combined with intravenous levofloxacin and amikacin, was successfully used to treat tuberculosis in a patient with severe digestive intolerance, highlighting a potential alternative regimen when standard oral therapy is not feasible. Full article

Objective: To evaluate the efficacy of the neurotropic action of cortexin in models of mental and physical developmental delays in rat offspring. Methods: The neurotropic properties of bovine brain cortex polypeptides were studied using two models of mental and physical developmental delays in rats: toxic CNS damage (oral administration of ethanol during the last week of pregnancy) and neonatal trauma (ischemia-hypoxia). The drug was administered intramuscularly or rectally as suppositories for 20 days. Treatment efficacy was evaluated using the mNSS scale, open field, rotarod, and adhesive removal tests. A histological examination of the brain was subsequently performed. In a separate series of experiments in mice, the concentration of the test drug cortexin and the reference drug cerebrolysin was determined in blood and brain tissue samples using radioactive iodine (Na125I) labeling of these preparations. Results: Modeling developmental delay in rat offspring (due to the toxic effect of ethanol in late pregnancy or neonatal trauma) led to pronounced neurological deficits, manifested by decreased motor activity, and sensorimotor, and coordination disorders. Administration of cortexin in all forms reduced the severity of neurological deficits as measured by mNSS scores, improved motor activity in the Open Field test, enhanced performance in the Adhesive Removal and Rotarod tests, and decreased structural changes in brain tissues. Histological examination revealed reduced neuronal damage in multiple cortical regions, with a significant increase in normal, unchanged neurons compared to placebo groups. Comparison of the blood concentrations of labeled Na125I cortexin depending on the type of administration showed similar distribution profiles in brain tissues, primarily dependent on its blood concentration, which was influenced by the route of administration. Conclusions: The results indicate that brain polypeptides (cortexin), administered either intramuscularly or rectally, can reach the systemic circulation and cross the blood-brain barrier, as demonstrated by our distribution studies using radiolabeled preparations. These polypeptides exert comparable neurotropic effects in models of mental and physical developmental delays in offspring caused by neonatal trauma or the toxic effect of ethanol in late pregnancy in rats. Full article

Transmucosal drug products, such as aerosols, films, semisolids, suppositories, and tablets, have been developed for the treatment of various human diseases and conditions. Transmucosal drug absorption is highly influenced by the biological structures of the mucosa and the physiological environment specific to the administration route (e.g., nasal, rectal, and vaginal). Over the last few decades, in vitro permeation testing (IVPT) using animal tissues or in vitro cell cultures have been utilized as a cost-effective and efficient tool for evaluating drug release and permeation behavior, assisting in formulation development and quality control of transmucosal drug delivery systems. This review summarizes the key mucosal permeation barriers associated with representative transmucosal administration routes, as well as considerations for IVPT method development. It highlights various IVPT methods, including vertical diffusion cell, flow-through diffusion cell, Ussing chamber, and transwell systems. Additionally, future perspectives are discussed, such as the use of optical methods to study in vitro drug permeation and the development of in vitro–in vivo correlation (IVIVC) for transmucosal drug development. The potential of IVPT as part of in vitro bioequivalence assessment strategies for locally acting transmucosal drug products is also highlighted. Full article

Introduction: The official implementation of pharmaceutical-grade cannabis raw materials for medicinal use has permitted doctors to prescribe and pharmacists to prepare cannabis-based formulations. The objective of the pharmaceutical development and manufacturing process optimization work was to propose a suppository formulation containing doses of 25 mg and 50 mg of tetra-hydrocannabinol (∆-9-THC) as an alternative to existing inhalable or orally administered formulations. The formulation could be used for rectal or vaginal administration, thereby providing dosage control in the treatment of endometriosis and other conditions involving pain. In this study, two substrates from suppositories with standardized Cannabis extractum normatum (CEX) were used: cocoa butter and Witepsol^® H15. Materials and Methods: The long-term stability of CEX was investigated over a period of up to 24 months. The concentrations of ∆-9-THC, cannabidiol (CBD), and cannabinol (CBN) were determined using an HPLC method. Furthermore, the water content of the extract, the ethanol residue, and the microbiological purity were determined. The pharmaceutical properties of CEX-incorporated suppositories, namely content uniformity, hardness, softening time, total deformation time, disintegration time, and the release profile of ∆-9-THC, CBD, and CBN, were evaluated in order to develop optimal preparation procedures for pharmacists. Results and Discussion: Following a 24-month stability study on CEX, no significant alterations in component content were observed beyond the specified requirements. The disintegration time, total deformation time, and hardness of the suppositories based on Witepsol^® H15 with CEX were found to be longer and higher, respectively, than those of suppositories formulated with cocoa butter. In vitro studies demonstrated that suppositories prepared with Witepsol^® H15 exhibited superior release of ∆-9-THC compared to those prepared with cocoa butter. Conclusions: We suggest that pharmacists making prescription drugs in a pharmacy setting in the form of medical marijuana suppositories will receive a better release profile of the drug by choosing Witepsol® H15 as a substrate. Full article

Objectives: This study aims to create an innovative self-microemulsifying drug delivery system (SMEDDS) suppository for ibuprofen (IBU) using semisolid extrusion (SSE) three-dimensional (3D) printing technology. Methods: Based on solubility studies and the ability to form a transparent microemulsion upon dilution, a selected oil, surfactant, and co-surfactant were utilized to prepare SMEDDS-3DPS containing IBU. The optimal formulation consisted of 10% Triacetin, 80% Gelucire 48/16, and 10% Tetraethylene glycol. SSE 3D printing was employed to create three different-sized suppositories with varying drug contents. These suppositories were assessed for their physicochemical properties, content uniformity, and dissolution profiles. Results: The prepared mixture exhibited suitable physical properties for printing, with nano-sized emulsion droplets providing a large surface area for improved drug absorption in the rectum. Characterization techniques such as differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy indicated that IBU was present in the formulation in an amorphous state. Additionally, in vitro dissolution tests demonstrated that SMEDDS-3DPS had a significantly higher initial dissolution rate compared with IBU powder. Conclusions: This research suggests that SMEDDS-3DPS, as a rectal IBU dosage form, can enhance the rectal bioavailability of IBU. It demonstrates the versatility of 3D printing as a novel manufacturing method for lipid-based suppositories and highlights the simplicity and adaptability of SSE 3D printing technology in producing customized suppositories tailored to individual patient needs, surpassing traditional methods. Full article

Research on the use of cannabis rectal suppositories for analgesia is limited. Few trials have evaluated the combined use of mindfulness and cannabis suppositories for anodyspareunia in men who have sex with men (MSM). This preliminary study, including a randomised control trial (RCT) and content analysis, assessed the effectiveness of an online mindful-compassion and cannabis suppository intervention among 52 British MSM (aged 18–50) who predominantly identified as bottoms (recipients of anal sex). Participants were randomly allocated to one of four groups based on whether they were using cannabis suppositories: adjunct cannabis suppository and mindful-compassion (CSMF), cannabis suppository only (CS), mindful compassion only (MF) and care as usual/control (CAU). Assessments measuring mindful compassion, sexual functioning, sexual self-efficacy, well-being, and anodyspareunia levels were completed at weeks 0, 4, and 12. Anodyspareunia levels were lower in the CSMF group compared to the other groups (CS/MF/CAU), p = 0.031. Feedback revealed that participants felt mindful compassion potentiated the effects of cannabis suppositories during sexual intimacy, reducing pain and enhancing sexual self-efficacy, sexual functioning, and well-being. This preliminary study warrants larger-scale investigation to establish the role of cannabis suppositories and mindful compassion in reducing anodyspareunia. Full article

Rectal drug administration could offer advantages in the delivery of medicines for children by avoiding swallowability issues, improving stability and enabling administration by caregivers. This study aimed to evaluate the rectal bioavailability of hollow-type suppositories (HTS) and understand the effect of two chemical forms of amoxicillin: amoxicillin sodium (AS) or amoxicillin trihydrate (AMT). HTS were prepared by incorporating a lipophilic core containing the antibiotic with a polyethylene glycol (PEG) shell. Formulations were characterised in vitro, and the absolute bioavailability was determined in a rabbit model, while drug–base interactions were evaluated using X-ray diffraction crystallography (XRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy. The in vitro amoxicillin release from AMT HTS was delayed, taking 27.3 ± 4.9 h to release 50% drug compared with 1.7 h for the AS HTS, likely due to solubility differences between AMT and AS. The presence of orthorhombic AMT and anhydrous AS crystals in respective HTS was confirmed via XRD and DSC. PEG shells were able to protect the drug chemical stability when stored at 25 °C/60% RH. Despite the difference in their in vitro release rates, a similar rectal bioavailability was found in both forms of amoxicillin (absolute bioavailability 68.2 ± 6.6% vs. 72.8 ± 32.2% for AMT HTS and AS HTS, respectively; p = 0.9682). Both HTS formulations showed little or no irritation to the rectal mucosa following a single dose. Full article

3D printing technology in medicine is gaining great attention from researchers since the FDA approved the first 3D-printed tablet (Spritam^®) on the market. This technique permits the fabrication of various types of dosage forms with different geometries and designs. Its feasibility in the design of different types of pharmaceutical dosage forms is very promising for making quick prototypes because it is flexible and does not require expensive equipment or molds. However, the development of multi-functional drug delivery systems, specifically as solid dosage forms loaded with nanopharmaceuticals, has received attention in recent years, although it is challenging for formulators to convert them into a successful solid dosage form. The combination of nanotechnology with the 3D printing technique in the field of medicine has provided a platform to overcome the challenges associated with the fabrication of nanomedicine-based solid dosage forms. Therefore, the major focus of the present manuscript is to review the recent research developments that involved the formulation design of nanomedicine-based solid dosage forms utilizing 3D printing technology. Utilization of 3D printing techniques in the field of nanopharmaceuticals achieved the successful transformation of liquid polymeric nanocapsules and liquid self-nanoemulsifying drug delivery systems (SNEDDS) to solid dosage forms such as tablets and suppositories easily with customized doses as per the needs of the individual patient (personalized medicine). Furthermore, the present review also highlights the utility of extrusion-based 3D printing techniques (Pressure-Assisted Microsyringe—PAM; Fused Deposition Modeling—FDM) to produce tablets and suppositories containing polymeric nanocapsule systems and SNEDDS for oral and rectal administration. The manuscript critically analyzes contemporary research related to the impact of various process parameters on the performance of 3D-printed solid dosage forms. Full article

Pentobarbital is a drug of choice to limit motion in children during paediatric procedural sedations (PPSs). However, despite the rectal route being preferred for infants and children, no pentobarbital suppositories are marketed, and therefore they must be prepared by compounding pharmacies. In this study, two suppository formulations of 30, 40, 50, and 60 mg of pentobarbital sodium were developed using hard-fat Witepsol^® W25 either alone (formulation F1) or with oleic acid (formulation F2). The two formulations were subjected to the following tests described in the European Pharmacopoeia: uniformity of dosage units, softening time, resistance to rupture, and disintegration time. The stability of both formulations was also investigated for 41 weeks of storage at 5 ± 3 °C using a stability-indicating liquid chromatography method to quantify pentobarbital sodium and research breakdown product (BP). Although both formulae were compliant to uniformity of dosage, the results were in favour of a faster disintegration of F2 compared to F1 (−63%). On the other hand, F1 was found to be stable after 41 weeks of storage unlike F2 for which several new peaks were detected during the chromatographic analysis, suggesting a shorter stability of only 28 weeks. Both formulae still need to be clinically investigated to confirm their safety and efficiency for PPS. Full article

Thermosensitive liquid suppositories (LSs) carrying the model antihypertensive drug metoprolol tartrate (MT) were developed and evaluated. The fundamental purpose of this work was to produce, for the first time, liquid MT suppositories based on biodegradable nanoparticles and optimize their rheological and mechanical properties for prospective rectal administration. The nanoparticle system was based on a biodegradable copolymer synthesized by ring opening polymerization (ROP) of glycolide (GL) and L,L-lactide (LLA). Biodegradable nanoparticles loaded with the model drug were produced by the o/o method at the first stage of the investigation. Depending on the concentration of the drug in the sample, from 66 to 91% of MT was released over 12 h, according to first-order kinetics. Then, thermosensitive LSs with MT-loaded biodegradable nanoparticles were obtained by a cold method and their mechanical and rheological properties were evaluated. To adjust the thermogelling and mucoadhesive properties for rectal administration, the amounts of major formulation components such as poloxamers (P407, P188), Tween 80, hydroxypropylcellulose (HPC), polyvinylpyrrolidone (PVP), and sodium alginate were optimized. The in vitro release results revealed that more than 80% of the MT was released after 12 h, following also first-order kinetics. It was discovered that the diffusion process was dominant. The drug release profile was mainly governed by the rheological and mechanical properties of the developed formulation. Such a novel, thermosensitive formulation might be an effective alternative to hypertension treatment, particularly for unconscious patients, patients with mental illnesses, geriatric patients, and children. Full article

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

Metronidazole-induced encephalopathy (MIE) is a rare and unpredictable complication that is most commonly reported in adults. Here, we present the case of MIE in a patient treated with rectal, oral, and intravenous metronidazole. This is the first case of MIE reported after suppositories. A 16-year-old girl with Crohn’s disease treated with mesalazine and exclusive enteral nutrition was operated on due to perianal fistulas and abscesses. She received oral metronidazole for 25 days and rectal metronidazole for 15 days as an adjuvant before surgery. Moreover, 2.5 g of intravenous metronidazole was administrated during the perioperative period. The second day after the surgery, symptoms of cerebellar syndrome appeared. She presented with an inability to coordinate balance and gait. Although she showed accurate verbal responses, her speech was slow, slurred, and scanning. The finger–nose test was positive. The T2-weighted magnetic resonance imaging revealed an increased symmetrical signal within the dentate nuclei of the cerebellum and in the corpus callosum. The changes were characterized by restricted diffusion. Based on the clinical picture and magnetic resonance imaging findings, MIE was diagnosed. Treatment with metronidazole was discontinued. The cumulative dose of metronidazole that she received for 29 days was 54 g: 38 g p.o., 13.5 g p.r., and 2.5 g i,v. The first symptoms appeared on the 28th day of antibiotic therapy after receiving 52 g of metronidazole. The neurological symptoms resolved after six days; however, three days after the resolution, paresthesia appeared in the distal phalanges of both feet and lasted for approximately two months. Our report highlights that neurologic symptoms related to metronidazole treatment should raise the suspicion of MIE. Full article

Two ways to deliver ultrasmall gold nanoparticles and gold-bovine serum albumin (BSA) nanoclusters to the colon were developed. First, oral administration is possible by incorporation into gelatin capsules that were coated with an enteric polymer. These permit the transfer across the stomach whose acidic environment damages many drugs. The enteric coating dissolves due to the neutral pH of the colon and releases the capsule’s cargo. Second, rectal administration is possible by incorporation into hard-fat suppositories that melt in the colon and then release the nanocarriers. The feasibility of the two concepts was demonstrated by in-vitro release studies and cell culture studies that showed the easy redispersibility after dissolution of the respective transport system. This clears a pathway for therapeutic applications of drug-loaded nanoparticles to address colon diseases, such as chronic inflammation and cancer. Full article

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development. Full article