Search Results (30)

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

The purpose of this study was to propose a new diagnostic approach using ultrasound imaging equipment. Many patients suffer from constipation, and medical professionals have difficulty providing treatment and care. The prevalence of constipation increases with age, and this condition strongly impacts the quality of life. Herein, a new diagnostic approach using ultrasound imaging equipment was examined. The study design was a narrative review, and the authors discussed existing knowledge, challenges, and prospects based on previous research. References were obtained by searching PubMed and Centralblatt für die gesammte Medicine. Most of the papers were published in English. Papers with scientific knowledge that has already been published in academic journals were extracted from these documents. No restrictions were placed on the publication date, sample size, study design, or age of subjects, and only published papers reporting scientific knowledge and consensus were cited. As a result, we suggest that this approach classifies the state of fecal retention in the rectum into three patterns. If ultrasound imaging indicates that the rectum is free of feces, there is no need to administer an enema. If hard stool is found, dissection can be performed to prevent complications such as severe intestinal perforation due to subsequent administration of laxatives. If ultrasound imaging reveals normal stool in the rectum, inducing defecation with suppositories may enable treatment for constipation. 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

The aim of this study was to prepare vaginal suppositories with mucoadhesive properties to prolong the action of antifungal component clotrimazole (CLO). This was achieved by preparing vaginal pessaries on a hydrophilic gel base composed of gelatin and gelatin enriched with PEG 400 (in a 1:1 ratio), and then checking the properties of the obtained vaginal drugs. The prepared globules, containing 100 mg of CLO, were characterized in terms of mass and swelling index, organoleptic analysis was also prepared. In addition, a texture analysis and a study of the dissolution of clotrimazole were performed. On the basis of the obtained results, it was concluded that the modification of the composition of the gelatin–glycerin base by the addition of macrogol had a positive effect on the mucoadhesive properties of the globules. In addition, due to the presence of PEG 400, the globules were stiffer. It was also observed that the presence of CLO reduces the value of the force needed for compression during the texture analysis study. Comparing the CLO release profiles of the prepared globules and commercially available clotrimazole tablets, the release profile for the globules was slower than for the tablets, which indicates the possibility of using mucoadhesive globules as a form of a drug that releases the medicinal substance more slowly at the site of administration. 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

Previous studies have shown that complexly shaped nanoparticles (NPs) have their intrinsic radiothermal emission in the millimeter range. This article presents a method for controlling the quality of nanodrugs—immunobiological preparations (IBPs)—based on the detection of their intrinsic radiothermal emissions. The emissivity of interferon (IFN) medicals, determined without opening the primary package, is as follows (µW/m²): IFN-α2b—80 ± 9 (10⁵ IU per package), IFN-β1a—40 ± 5 (24 × 10⁶ IU per package), IFN-γ—30 ± 4 (10⁵ IU per package). The emissivity of virus-like particles (VLP), determined using vaccines Gam-VLP-multivac (120 μg) in an injection bottle (crimp cap vials), was as follows: 12 ± 1 µW/m², Gam-VLP—rota vaccines—9 ± 1 µW/m². This study shows the reproducibility of emissivity over the course of a year, subject to the storage conditions of the immunobiological products. It has been shown that accelerated aging and a longer shelf life are accompanied by the coagulation of active NPs, and lead to a manyfold drop in emissivity. The dependence of radiothermal emission on temperature has a complex, non-monotonic nature. The emission intensity depends on the form of dosage, but remains within the order of magnitude for IFN-α2b for intranasal aqueous solution, ointments, and suppositories. The possibility of the remote quantitative control of the first phases of the immune response (increased synthesis of IFNs) to the intranasal administration of VLP vaccines has been demonstrated in experimental animals. Full article

Respiratory tract infections (RTIs) are usually characterized by mucus hypersecretion. This condition may worsen and prolong symptoms and signs. For this reason, reducing mucus production and improving mucus removal represent relevant aspects of managing patients with RTIs. In this regard, mucoactive drugs may be effective. Mucoactive agents constitute a large class of compounds characterized by different mechanisms of action. Sobrerol is a monoterpene able to fluidify mucus, increase mucociliary clearance, and exert antioxidant activity. Sobrerol is available in various formulations (granules, syrup, nebulized, and suppository). Sobrerol has been on the market for over 50 years. Therefore, the present article revised the evidence concerning this compound and proposed new possible strategies. The literature analysis showed that several studies investigated the efficacy and safety of sobrerol in acute and chronic RTIs characterized by mucus hyperproduction. Seven pediatric studies have been conducted with favorable outcomes. However, the regulatory agencies recently reduced the treatment duration to three days. Therefore, a future study will test the hypothesis that a combination of oral and topical sobrerol could benefit children and adults with frequent respiratory tract infections. The rationale of this new approach is based on the concept that mucus accumulation could be a risk factor for increased susceptibility to infections. 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

The current study describes a suppository base composed of aqueous gelatin solution emulsifying oil globules with probiotic cells dispersed within. The favorable mechanical properties of gelatin to provide a solid gelled structure, and the tendency of its proteins to unravel into long strings that interlace when cooled, lead to a three-dimensional structure that can trap a lot of liquid, which was exploited herein to result in a promising suppository form. The latter maintained incorporated probiotic spores of Bacillus coagulans Unique IS-2 in a viable but non-germinating form, preventing spoilage during storage and imparting protection against the growth of any other contaminating organism (self-preserved formulation). The gelatin–oil–probiotic suppository showed uniformity in weight and probiotic content (23 ± 2.481 × 10⁸ cfu) with favorable swelling (double) followed by erosion and complete dissolution within 6 h of administration, leading to the release of probiotic (within 45 min) from the matrix into simulated vaginal fluid. Microscopic images indicated presence of probiotics and oil globules enmeshed in the gelatin network. High viability (24.3 ± 0.46 × 10⁸), germination upon application and a self-preserving nature were attributed to the optimum water activity (0.593 a_w) of the developed composition. The retention of suppositories, germination of probiotics and their in vivo efficacy and safety in vulvovaginal candidiasis murine model are also reported. Full article

Pharmaceutical compounding using the molding technique is the currently applied method for the on-demand manufacturing of suppositories and pessaries. Potential errors of this method are difficult to detect, and the possibilities of individualization of size and shape of the suppositories are limited. In this study, a syringe-based semi-solid 3D printing technique was developed for the manufacturing of suppositories in three different printing designs with the suppository bases polyethylene glycol (PEG) and hard fat (HF). The 3D printed suppositories were analyzed for their visual appearance, uniformity of mass and content, diametrical dimension, breaking force and release behavior and compared to suppositories of the same composition prepared by a commonly used molding technique. The results showed no adverse properties for the 3D printed suppositories compared to the molded ones. Moreover, the easy adaptation of shape using the 3D printing technique was demonstrated by the printing of different sizes and infill structures. Thus, 3D printing has great potential to complement the available manufacturing methods for compounded suppositories, as it represents an automated system for the individualized manufacturing of suppositories that meet patients’ needs. 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

Bacterial vaginosis, a polymicrobial clinical syndrome characterized by a shift in healthy vaginal microbiota due to bacterial colonization, is characterized by high recurrence rates after conventional treatment with an antimicrobial agent. This has necessitated the need to develop a formulation that has the potential to ensure Lactobacilli viability and bacterial clearance. This study seeks to develop and optimize a layered suppository using a five-level central composite design to ensure optimized metronidazole release and lactic acid viability. Layered suppositories were formulated using the fusion method using polyethylene glycol blend 1500/4000 and Ovucire^® as suppository bases. Lactobacillus fermentum was incorporated in the molten mass before molding the solid body suppositories into the cavity of hollow-type suppositories and sealing the molten excipients. Artificial neural network model predictions for product optimization showed high predictive capacity, closely resembling experimental observations. The highest disintegration time recorded was 12.76 ± 0.37 min, with the optimized formulations showing lower times of 5.93 ± 0.98 min and an average weight of 1.17 ± 0.07 g. Histopathological observations determined high compatibility of suppositories with vaginal cells with no distortion or wearing of the vagina epithelium. This optimized formulation provides a safe and promising alternative to conventional suppositories in the treatment and prevention of the recurrence of bacterial vaginosis. 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