Evaluation of the Physical-chemical Characteristics and Biopharmaceutical Performance of Dilu-Cap: A Complete Line of Excipients for Hard-shell Capsules.

The development of an efficient formulation for hardshell capsules needs to consider pharmaceutical and biopharmaceutical aspects to assist in the careful selection of excipients, which are essential ingredients for the formulation's good performance. They ensure correct bioavailability, solubility, stability, dose accuracy (weight variation and content uniformity), and organoleptic characteristics. Given this, DiluCap was developed as a line of excipients so that the pharmacist can compound every capsule formulation with ease and trust in its final characteristics. The line is composed of six excipients: 1) Dilucap SLD, for soluble active pharmaceutical ingredients Class I and III from the Biopharmaceutical Classification System - it promotes disintegration without a negative impact on dissolution; 2) Dilucap PSD, for poorly soluble active pharmaceutical ingredients Class II and IV - it favors the disintegration and dissolution of the active pharmaceutical ingredients; 3) Dilucap SR, for active pharmaceutical ingredients requiring modified/ slow release - it reduces the disintegration and release rate of the active pharmaceutical ingredients, promoting its slow release, and, also, prevents plasma peaks responsible for adverse effects; 4) DiluCap Hygro, for hygroscopic or deliquescent active pharmaceutical ingredients - it reduces hygroscopicity, deliquescence, and eutectic mixture formation; 5) DiluCap Antioxi, for active pharmaceutical ingredients susceptible to oxidation - it provides chemical stabilization due to antioxidant ingredients and reduces water activity and chemical degradation; 6) DiluCap OD, for orodispersible active pharmaceutical ingredients that can be compounded as sprinkle capsules or sublingual capsules - it favors transmucosal permeation. The testing conducted for the DiluCap line of excipients showed that all products have suitable flow properties (angle of repose and Carr's compressibility index), hygroscopicity, biopharmaceutical performance (dissolution profiles), and stability. This corroborates the allegations that DiluCap provides a science based line of excipients to the compounding pharmacies with proven functionality that saves time (reduces the preprocessing and the number of items in stock) and guarantees efficacy and safety of hard-shell oral capsules formulations.

Compatibility of Gestrinone, Nimesulide, and Piroxicam in Pentravan for Transdermal and Transmucosal Application.

Transdermal products are intended to be applied topically but to promote the biological effects systemically, while transmucosal products have the same final effect but are to be applied on mucosa (for example, vaginal mucosa). The extension and velocity in which absorption occurs vary depending on the vehicle used, the active pharmaceutical ingredient and a broad range of other factors related to the formulation, patient, and environmental characteristics. Ready-to-use vehicles, such as Pentravan, with proven penetration efficacy for various active pharmaceutical ingredients, are paramount. Pentravan, specially developed for compounding pharmacies, has been extensively studied. To date, most studies have focused on endocrinology (e.g., sexual hormones), anti-aging strategies, and gynecology (endometriosis and related conditions). In this work, we have determined the compatibility of Pentravan and three active pharmaceutical ingredients: gestrinone, a steroidal substance for vaginal use (endometriosis), and nimesulide and piroxicam, two nonsteroidal anti-inflammatory drugs used both for topical and vaginal application. This article shows an excellent beyond-use date of 180 days when stored at room temperature, which renders it suitable for daily practice.

Characterization and Safety Profile of Transfer Factors Peptides, a Nutritional Supplement for Immune System Regulation.

Imuno TF® is a nutritional supplement composed of isolated transfer factors (TF) from porcine spleen. It is composed of a specific mixture of molecules that impact functions of the biological systems and historically is linked to the immune system regulation. In this study, we demonstrate for the first time its proteomic analysis, nutritional composition, and safety profile in terms of mutagenic potential and acute oral dose (LD50). The obtained analysis indicated the product is a complex set of oligo- and polypeptides constituted of 163 different peptides which can potentially act on multiple mechanisms on the immune system pathways. The chemical composition showed low fat and low sugar content, saturated fatty acids-free, and the presence of 10 vitamins and 11 minerals. No mutagenic effect was observed, and the LD50 was 5000 mg kg-1 body weight. This accounts for a safe product to be used by the oral route, with potential benefits for the immune system.

Always the Right Dose? Content Uniformity in Over 100 Different Formulations Tested.

There is still an evident need for nonsterile compounded medications for pediatric and elderly patients in cases where patients require dose adjustments or have swallowing difficulties. Pharmacists generally have the choice between compounding capsules or oral liquids. In daily pharmacy practice, extemporaneous capsules are from time to time seen as a better alternative to oral liquid medication, although various published studies indicate that weight variation and/or uniformity of content can be significantly out of specification for compounded capsules. In contrast, analyses with the ready-to-use oral liquid vehicle SyrSpend SF in 104 different formulations with 89 unique active pharmaceutical ingredients showed results that all 6.414 samples analyzed were within specification. It can, therefore, be argued that SyrSpend SF could be a better way to assure content uniformity compared to manually compounded, small-batch extemporaneous capsules.

Stability of Azathioprine, Clonidine Hydrochloride, Clopidogrel Bisulfate, Ethambutol Hydrochloride, Griseofulvin, Hydralazine Hydrochloride, Nitrofurantoin, and Thioguanine Oral Suspensions Compounded with SyrSpend SF pH4.

To allow for tailored dosing and overcome swallowing difficulties, compounded liquid medication is often required in pediatric patients. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients azathioprine (powder) 50 mg/mL, azathioprine (from tablets) 50 mg/mL, clonidine hydrochloride (powder) 0.1 mg/mL, clopidogrel bisulfate (from tablets) 5 mg/mL, ethambutol hydrochloride (powder) 50 mg/mL, ethambutol hydrochloride (from tablets) 50 mg/mL, ethambutol hydrochloride (powder) 100 mg/mL, griseofulvin (powder) 25 mg/mL, hydralazine hydrochloride (powder) 4 mg/mL, nitrofurantoin (powder) 10 mg/mL, and thioguanine (powder) 2.5 mg/mL. Suspensions were compounded at the concentrations listed above and stored at controlled room and refrigerated temperatures. Stability was assessed by measuring the percentage recovery at 0 day (baseline), and at 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography, via a stability-indicating method. The following oral suspensions compounded using SyrSpend SF PH4 as the vehicle showed a beyond-use date of 90 days when stored both at room or refrigerated temperatures: clonidine hydrochloride 0.1 mg/mL, ethambutol hydrochloride 50 mg/mL and 100 mg/mL, griseofulvin 25 mg/mL, nitrofurantoin 10 mg/mL, and thioguanine 2.5 mg/mL, all compounded from the active pharmaceutical ingredients in powder form. Suspensions compounded using the active pharmaceutical ingredients from tablets presented a lower beyond-use date: 30 days for ethambutol hydrochloride 50 mg/mL and hydralazine hydrochloride 4 mg/mL, stored at both temperatures, and for clopidogrel bisulfate 5 mg/mL when stored only at refrigerated temperature. Azathioprine suspensions showed a beyond-use date of 14 days when compounded using active pharmaceutical ingredients in powder form at both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

Transdermal Delivery of Metformin Hydrochloride from a Semisolid Vehicle.

Metformin hydrochloride is a traditional, FDA-approved drug used as a first-line drug of choice to treat type 2 diabetes. Research has shown metformin hydrochloride effective in injuries, including age-related maladies. The purpose of this ex vivo study was to evaluate the use of a commercial transdermal vehicle as a semisolid, liposomal vanishing cream (Pentravan) to deliver metformin hydrochloride through the human skin. The experiments were conducted as percutaneous absorption assay in Franz Diffusion Cells, coupled with freshly excised human skin and analyzed by high-performance liquid chromatography. Both methods were based on validated methods of both the United States Pharmacopeial Convention, Inc. and the International Conference on Harmonization. A 46.7% permeation percentage was found, with a drug flux of 3.91 µg cm-2 h-1 and a lag time of 0.51 h, following pseudo first-order absorption kinetics. These results showed that transdermal metformin hydrochloride can be an option for patients searching for diverse clinical effects.

Compounded Orodispersible Films with Natural Ingredients for Halitosis: A Clinical Experience.

Halitosis can be described as unpleasant odors emanating from the oral cavity. It is usually associated with decomposition action of bacteria present mainly on the back of the tongue and periodontal pockets, and able to produce volatile sulfur compounds. We conducted a study at the Faculty of Dentistry, Federal University of Juiz de Fora and evaluated the therapeutic effect of two natural extracts, Camellia sinensis (green tea) and resveratrol in the form of oral polymer films, to control halitosis. Fifty volunteers (students of health courses) participated in the research after orientation and signing the informed consent form. The anamnesis was made by researchers. The physical examination was made to verify the inclusion criteria. Each participant received 45 polymeric films to be consumed in 15 days (3 films per day). Measurements of the volatile sulfur compound levels were performed using a halimeter in two stages: 1) before use and 2) 15 days after the first administration. Results showed a statistically significant reduction in volatile sulfur compound levels in 71.79% of the volunteers. We concluded that the compounded orodispersible films containing green tea and resveratrol demonstrated excellent results in reducing halitosis.

Compatibility of Baclofen, Carvedilol, Hydrochlorothiazide, Mercaptopurine, Methadone Hydrochloride, Oseltamivir Phosphate, Phenobarbital, Propranolol Hydrochloride, Pyrazinamide, Sotalol Hydrochloride, Spironolactone, Tacrolimus Monohydrate, Ursodeoxycholic Acid, and Vancomycin Hydrochloride Oral Suspensions Compounded with SyrSpend SF pH4.

Compounded liquid medication is frequently required in children to allow easy dose adjustment and overcome swallowing difficulties. The objective of this study was to evaluate the stability of oral suspensions compounded with SyrSpend SF PH4 and the commonly used active pharmaceutical ingredients baclofen 2.0 mg/mL, carvedilol 5.0 mg/mL, hydrochlorothiazide 2.0 mg/mL, mercaptopurine 10.0 mg/mL, methadone hydrochloride 10.0 mg/mL, oseltamivir phosphate 6.0 mg/mL, phenobarbital 9.0 mg/mL and 15.0 mg/mL, propranolol hydrochloride 0.5 mg/mL and 5.0 mg/mL, pyrazinamide 100.0 mg/mL, spironolactone 2.0 mg/mL and 2.5 mg/mL, sotalol hydrochloride 5.0 mg/mL, tacrolimus monohydrate 0.5 mg/mL, ursodeoxycholic acid 20.0 mg/mL, and vancomycin hydrochloride 25.0 mg/mL. Suspensions were compounded with raw powders, except for mercaptopurine, pyrazinamide, and sotalol hydrochloride, which were made from commercial tablets. Stability was assessed by measuring the percentage recovery at 0 (baseline), 60 days, and 90 days after compounding for suspensions made with raw powders, which were stored at 2ÅãC to 8ÅãC. The stability of tablets, which were stored at 2ÅãC to 8ÅãC and 20ÅãC to 25ÅãC, was assessed by measuring the percentage recovery at 0 (baseline), 7 days, 14 days, 30 days, 60 days, and 90 days. Active pharmaceutical ingredients quantification was performed by ultraviolet high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions in the conditions tested. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

Stability of Acetazolamide, Baclofen, Dipyridamole, Mebeverine Hydrochloride, Propylthiouracil, Quinidine Sulfate, and Topiramate Oral Suspensions in SyrSpend SF PH4.

The objective of this study was to evaluate the stability of 7 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): acetazolamide 25.0 mg/mL, baclofen 10.0 mg/mL, dipyridamole 10.0 mg/mL, mebeverine hydrochloride 10.0 mg/mL, propylthiouracil 5.0 mg/mL, quinidine sulfate 10.0 mg/mL, and topiramate 5.0 mg/mL. All suspensions were stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by measuring the percentage recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredient quantification was performed by ultraviolet (UV) high-performance liquid chromatography, via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredient + vehicle) was at least 90 days for all suspensions with regards to both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

Permeation profiles of resveratrol cream delivered through porcine vaginal mucosa: Evaluation of different HPLC stationary phases.

Trans-resveratrol affects biological systems in a multitude of ways, but its oral bioavailability is remarkably poor due to in vivo metabolization. This drawback has fomented the development of new strategies for systemic delivery, such as transmucosal delivery via the vaginal route, which is our main focus here. In this sense, our pioneering study purposed to evaluate the trans-resveratrol permeation efficacy through this route. For that, we used a previously validated method and tested it with three different stationary phases: a commercial C18 column and two laboratory-made chromatographic columns containing poly(methyloctadecylsiloxane) (PMODS) thermally immobilized onto zirconized silica (Zr-PMODS) or titanized silica (Ti-PMODS). The permeation experiments showed that resveratrol, in the formulation used, was not successfully delivered to the bloodstream - it was actually retained within the vaginal mucosa, which suggests a local use rather a systemic one.

Pharmaceutical development of enteric-release hard gelatin capsules in the compounding setting.

Enteric coated capsules are characterized by their resistance to dissolution in low pH environments, such as the stomach, and by their rapid disintegration in a higher pH environment, such as the intestine. The surface of hard gelatin capsules is usually smooth and nonporous, which limits their coating efficiency. We developed a simple, quick, and easily reproducible compounding preparation method for enteric-release hard gelatin capsules. Twenty-two batches of 60 diclofenac sodium capsules each were prepared and then divided into three groups. Each group was submitted to a different coating process using a small-scale enteric coating machine and a coating process based on the atomization (spraying) of organic solutions of polymers. The results of dissolution testing were compared statistically within the groups and also with a reference drug control (Voltaren DR). Some of the batches in group I and all the batches in groups II and III met the pharmacopeial requirements for enteric release, in both acid and pH 6.8 phosphate buffer stages. Dissolution of capsules coated with Eudragit L100 was more efficient than that of other tested systems (P less than 0.05). The dissolution assay results for group III in the acid stage were superior to the results for the reference drug, but no statistical difference was noticed between these two in the phosphate buffer stage. Diclofenac sodium hard gelatin capsules coated with cellulose acetate Phthalate or Eudragit L100 presented dissolution performance that met pharmacopeial requirements. Furthermore, results obtained with Eudragit-coated capsules were comparable to those obtained with the reference drug.