International journal of pharmaceutical compounding最新文献

Geriatric patients have difficulty to comply to their medication regimen due to complicated medication administration schedule, dysphagia, reduced ability to swallow tablets and dementia. This is particularly more challenging among the Alzheimer Disease's patients. Therefore, a model drug, memantine hydrochloride has been formulated into an orally disintegrating film (ODF) for easier consumption. However, bitter taste of memantine hydrochloride needs to be solved first if the drug is formulated into an ODF. The objective of this study is to taste mask memantine hydrochloride ODF and conduct a palatability study to evaluate the palatability of the dosage form. Memantine hydrochloride ODF was prepared using solvent casting method followed by freeze drying. The polymeric base consisted of Guar gum, PEG 400 and wheat starch in solvent water, with varying amounts of Aspartame or Acesulfame K for taste masking. The freeze-dried memantine hydrochloride ODFs were evaluated for tensile strength, in-vitro disintegration time, average thickness, dissolution, memantine hydrochloride content, and palatability. Formulation M7 was selected as the best taste masked formulation. Aspartame 30 mg is sufficient to cover the bitter taste of memantine hydrochloride in ODF form. A taste masked memantine hydrochloride ODF of dimensions 20 x 20 mm containing 30mg of aspartame was successfully developed. This formulation has average values for tensile strength 0.03 (0.01) kPa, folding endurance 351.92 (4.82) flips, thickness 0.94 (0.02) mm, and disintegration time 34.15 (2.16) seconds.

Compounding pharmacies commonly use ready-to-use vehicles such as TrichoSolTM to produce hair solutions for alopecia. However, chemical and microbiological compatibility are paramount to be determined so those can be safely implemented as the vehicle of choice. This study aimed to assess the physical-chemical and microbiological stabilities of selected active pharmaceutical ingredients in TrichoSolTM. For that, HPLC analyses and Antimicrobial Effectiveness Testing were conducted in bracketed studies. The beyond-use dates (BUDs) found were: 180 days for cetirizine hydrochloride 0.5%-2.0%, dutasteride 0.1%, hydrocortisone acetate 0.5%, nicotinamide 0.25%-0.50%, progesterone 1.0%, and pyridoxine hydrochloride 0.25%-5.0%. BUDs of 150 days were observed for hydrocortisone acetate 1.0%, 120 days for Dutasteride 0.25%, and 90 days for progesterone 2.5%.

Compounders worldwide are responsible for ensuring that the sterile preparations they dispense are pure, potent, and safe. To achieve that result, proper cleaning and disinfection of International Organization for Standardization controlled environments must occur. Because those tasks must be performed according to established standards, the compounding pharmacist must research regulatory requirements and appropriate products for use. In this report, we focus on U.S. regulations, guiding entities, and effective products that enable compliance with the increasingly stringent procedures required for pharmaceutical compounding. We also review cleaning and disinfecting processes, discuss the importance of correctly choosing and using disinfectants and/ or sporicidal disinfectants with surface claims in the cleanroom, and provide answers to questions frequently asked by staff who use those agents. In addition, we profile specific disinfectants that are compliant with United States Pharmacopeia Chapter <797> and current good manufacturing practice standards. Biological safety cabinets and compounding aseptic containment isolators must undergo an additional process that deactivates hazardous drug residues and removes them from the interior surfaces of those devices before they are cleaned and disinfected, but that discussion is beyond the scope of this article.

Allopurinol is a xanthine oxidase inhibitor used to reduce the production of uric acid in the body. Commercial tablets may be crushed and suspended in a compounding vehicle and provide an alternative dosage form for patients with difficulty swallowing, such as children. The stability of a compounded preparation of allopurinol 20 mg/mL was evaluated in ready-to-use vehicles, namely Oral Mix and Oral Mix SF. A stability indicating HPLC method was developed and validated to assess the amount of allopurinol over time. Formulations were stored in tightly closed, light resistant plastic containers at both room temperature and refrigerated conditions. Chemical analysis, pH measurement and organoleptic assessment were performed at predetermined time points up to 90 days. Antimicrobial effectiveness testing was also performed after 90 days of storage at room temperature. The stability study demonstrated that the allopurinol 20 mg/mL suspensions prepared from commercial tablets in Oral Mix and Oral Mix SF was stable up to 90 days under the tested conditions.

Purpose: Healthcare providers often need to explore alternative options for patients who are unable to swallow whole tablets or capsules. Many newly approved immediate-release (IR) solid oral drugs carry a general "do-not-crush" warning or similar statements in their labeling without any explanations. A 2021 publication by Uttaro et al. presented a crushability analysis strategy for risk assessment and demonstrated its utility for some uncertain IR drugs on the ISMP do-not-crush list. This article provides an update on the topic and performs the crushability analysis of newly FDA-approved drugs.

Methods: The novel drug approvals from 2020-22 were obtained from the FDA website. The IR oral tablets and capsules were extracted from the lists and subjected to crushability analysis. The scope of crushing activity was defined as crushing the tablets or capsule contents using a mortar and pestle, followed by suspending the powder in plain water at room temperature and administering the dose within 2 hours. The crushability analysis employed a checklist of questions regarding special dosage form design, hazardous drug status, stability & pharmacokinetics (PK), unofficial data from manufacturers, and availability of alternative dosage forms. The FDA-approved product labels were used as the main references for the analysis. NIOSH publications, FDA Orange Book, patents, and scientific literature were used for selected drugs.

Results: From 2020 to 2022, 52 novel drug approvals were identified as IR oral tablets and capsules. Among them, 2 products were discontinued, and 10 already included specific manipulation instructions on their labels. The remaining 40 products had either a general "do-not-crush" statement or no information regarding crushability on the labels. The crushability analysis of these 40 products revealed that 23 products exhibited a low risk for crushing. However, the remaining 17 products were not suitable for crushing due to mostly stability/PK concerns. Four manufacturers had unofficial data related to crushing or mixing with liquids/soft foods, and none of the products had alternative oral liquid dosage forms.

Conclusion: The crushability analysis strategy was updated and applied to 40 IR oral tablets and capsules approved by FDA during 2020-22. The summary table and highlighted examples serve as a practical resource for pharmacists and other healthcare providers to make informed decisions regarding dosage form manipulation to facilitate dose administration in patients with difficulty swallowing solids.

There are minimum levels of water activity that are required for growth of bacteria and molds. Water activity is the ratio of vapor pressure of water in a product to pure water at the same temperature. Pure distilled water has a water activity of 1. Water activity is also a measure of water in a material that is available to react with or attach itself to other material; it is also called "free" water while the unavailable water is called "bound" water. Higher water activity substances tend to support more microorganisms; bacteria usually require water activity values of at least 0.91 and fungi at least 0.6. Every microorganism has a limit of water activity below which it will not grow. To lower water activity, one can add or change the concentrations of ingredients such as sodium chloride, sucrose, alcohol, propylene glycol, or glycerin so the preparation becomes self-preserving. Also, if the preparation has too high a water activity and the addition of other substances to lower the water activity, then a preservative may be required for the preparation. Nonaqueous liquids or dry solids will not support spore germination or microbial growth due to their low water activity.

Water is the most abundant substance on earth, covering about 70% of the earth's surface. Life is dependent upon water and the water cycles involved. In pharmaceutical compounding, water is the most widely used excipient employed as a solubilizing agent and as a vehicle; it is also used medicinally. With the variety in dosage forms, there are different types of waters that are used, some with specific uses and some more general. For the different types or categories of water, there are different methods of preparation, different characteristics, and different properties that can be used as an advantage in compounding. This article describes the different categories of waters, their use, preparation, characteristics, and water chemistry in general.

Background: This study investigates the compatibility and stability of active pharmaceutical ingredients (APIs) in Cleoderm™, a dermatological cream designed for the treatment of acne vulgaris, hyperpigmentation, dermatitis and other skin conditions. Cleoderm™ is formulated with hyaluronic acid and Cleome gynandra L., recognized for their sebum-regulating and anti-inflammatory properties. Complementary ingredients, such as palmitoyl tripeptide-8, bisabolol, and functional oils, contribute to the cream's antioxidant and anti-inflammatory effects.

Method: High-performance liquid chromatography (HPLC) was employed to assess the compatibility of APIs in Cleoderm™. Forced degradation studies were conducted to evaluate API stability under diverse stress conditions.

Result: The study established beyond-use dates (BUDs) for the tested formulations stored at room temperature. Adapalene (0.1%), dapsone (5% to 10%), and hydroquinone (10%) exhibited BUDs of 180 days. Throughout this period, no discernible physical alterations were observed in the formulations, and their chemical stability remained within acceptable parameters. Comprehensive microbiological assessments affirmed the efficacy of the preservative system.

Conclusion: These findings underscore Cleoderm™'s potential as a dependable vehicle for compounded dermatological preparations. The study underscores the significance of continuous stability assessments and quality control protocols in formulating personalized and efficacious treatments for acne vulgaris and other inflammatory dermatoses. Progress in this field holds promise for enhancing therapeutic options and outcomes for individuals affected by these conditions.

Non-compliance is a serious healthcare issue. It contributes to waste of medication, deterioration of patient's quality of life and increase in healthcare cost. It is challenging to ensure Alzheimer's disease patients to comply to their medication daily. Hence, patient friendly and innovative dosage form is required to overcome the challenges. Orally disintegrating film (ODF) is proposed as solution to non-compliance. The objective of this research was to compare oven drying and freeze drying process on the physical properties of memantine hydrochloride ODF. A central composite design was used. The factors considered were concentration of Guar Gum (0.5-1.84g), concentration of wheat starch (0.5-1.84g) and concentration of PEG 400 (0.5-1.84g). A total of 20 formulations for each drying method were prepared. The ODFs produced were then characterized using uniformity of thickness tensile strength, folding endurance, disintegration time test. The optimum formulation was selected and incorporated with memantine hydrochloride. A flexible Memantine hydrochloride ODF formulation with fast disintegration time, sufficient mechanical strength and stable over a period of six months was successfully developed. The optimum formulation has 1.50 g guar gum, 1.50 g starch and 1.50 g of PEG 400. Freeze dried films are preferred as these films are more flexible and porous that lead to faster disintegration time. The findings suggest that memantine hydrochloride ODF has the potential as an alternative dosage form in treating Alzheimer's disease.