Quality by design approach for fabrication of extended-release buccal films for xerostomia employing hot-melt extrusion technology.

The study endeavors the fabrication of extended-release adipic acid (APA) buccal films employing a quality by design (QbD) approach. The films intended for the treatment of xerostomia were developed utilizing hot-melt extrusion technology. The patient-centered quality target product profile was created, and the critical quality attributes were identified accordingly. Three early-stage formulation development trials, complemented by risk assessment aligned the formulation and process parameters with the product quality standards. Employing a D-optimal mixture design, the formulations were systematically optimized by evaluating three formulation variables: amount of the release-controlling polymer Eudragit® (E RSPO), bioadhesive agent Carbopol® (CBP 971P), and pore forming agent polyethylene glycol (PEG 1500) as independent variables, and % APA release in 1, 4 and 8 h as responses. Using design of experiment software (Design-Expert®), a total of 16 experimental runs were computed and extruded using a Thermofisher ScientificTM twin screw extruder. All films exhibited acceptable content uniformity and extended-release profiles with the potential for releasing APA for at least 8 h. Films containing 30% E RSPO, 10% CBP 971P, and 20% PEG 1500 released 88.6% APA in 8 h. Increasing the CBP concentration enhanced adhesiveness and swelling capacities while decreasing E RSPO concentration yielded films with higher mechanical strength. The release kinetics fitted well into Higuchi and Krosmeyer-Peppas models indicating a Fickian diffusion release mechanism.

A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing.

Hot-melt extrusion (HME) has been extensively investigated for continuous manufacturing of amorphous solid dispersions, to improve the solubility of poorly water-soluble drug substances, impart abuse deterrence to controlled substances, taste masking for pediatric and geriatric formulations and development of cocrystal system. Much research has been conducted on the continuous manufacturing of solid dosage forms using HME, but its applicability in the manufacturing of semisolids remains an unexplored domain. This study aimed to explore the applicability of HME in the continuous manufacturing of topical semi-solid formulations with two active pharmaceutical ingredients (APIs). Ointments containing a combination of triamcinolone acetonide and lidocaine hydrochloride were screened based on a quality target product profile (QTPP) and established critical quality attributes (CQAs) using design of experiments (DoE). Three selected formulations, manufactured by a lab-scale fusion method and HME, were subjected to further characterization studies including work of adhesion, stiffness, apparent pH, content uniformity, differential scanning calorimetry, accelerated stability, and in vitro drug release testing. Selected formulations met design characteristics and demonstrated the applicability of HME in the continuous manufacturing of semi-solid formulations. Graphical abstract.

Role of the pharmacist in preventing distribution of counterfeit medications.

OBJECTIVE: To provide an overview of the counterfeit medication problem and recommendations of a joint American Pharmacists Association (APhA) Academy of Pharmaceutical Research and Science and APhA Academy of Pharmacy Practice and Management taskforce. DATE SOURCES: SciFinder and PubMed were searched from 1980 to March 2011 using the following keywords: counterfeit drug product, counterfeit medications, drug product authentication, drug product verification, and track-and-trace. Publications, presentations, and websites of organizations that research the counterfeit medication problem in the United States and other countries were reviewed. A representative from the security division of a pharmaceutical manufacturer and a representative from a supplier of anticounterfeiting technologies gave presentations to the taskforce. SUMMARY: The taskforce recommends that pharmacists (1) purchase medications from known, reliable sources; (2) warn patients of the dangers of purchasing medications over the Internet; (3) confirm with distributors that products were purchased from manufacturers or other reliable sources; (4) monitor counterfeit product alerts; (5) examine products for suspicious appearance; (6) work with the pharmaceutical industry, distributors, and the Food and Drug Administration (FDA) to close gaps in the supply chain, especially for drugs in short supply; (7) use scanning technology in the pharmacy as part of a prescription verification process; (8) educate themselves, coworkers, and patients about the risks of counterfeit medications; and (9) report suspicious medications to FDA, the distributor, and the manufacturer. CONCLUSION: The consequence of a patient receiving a counterfeit medication in the United States could be catastrophic, and pharmacists must play an active role in preventing such an event from occurring.

Effect of a proprietary Magnolia and Phellodendron extract on weight management: a pilot, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To determine the efficacy of a dietary supplement ingredient containing proprietary extracts of Magnolia officinalis and Phellodendron amurense in helping overweight, otherwise healthy, premenopausal female adults, who typically eat more in stressful situations manage their body weight. DESIGN: Randomized, double-blind, placebo-controlled clinical study. Setting Miami Research Associates, a clinical research organization consisting of 32 board-certified physicians, Miami, Fla. SUBJECTS: Healthy, overweight (BMI 25 to 34.9), premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scored above the national mean for women on self-reported anxiety. INTERVENTIONS: Two-hundred-fifty-mg capsules or identical placebo capsules 3 times a day for 6 weeks. MAIN OUTCOME MEASURES: Salivary cortisol levels, weight change, psychological measures of stress and anxiety. RESULTS: Twenty-eight subjects completed the study. Extracts of M officinalis and P amurense were well tolerated. There was a significant weight gain during the study for the placebo group (P < ,01), but no significant weight gain for the group receiving extracts of M officinalis and P amurense (P < .89). Paired t-tests comparing baseline to post-treatment weight showed an average gain of 1.5 kg in the placebo group and no change in the treatment group (P = .89). When groups were divided into gainers (ie, participants who gained at least 1 kg or more) and maintainers or losers, 75% of the control group were gainers versus 37% of the treatment group (P < .04). There was a nonsignificant trend for lowered average cortisol in the treatment group at the end of the study (group X time interaction, F = 1.1, P < .15). This difference was due to a treatment effect on evening cortisol. There was a marginally significant group X time interaction (P = .06), showing the treatment group tended to have lower levels of cortisol in the evening, whereas the control group tended to have higher levels of cortisol in the evening. Bedtime cortisol levels decreased in the treatment group and increased in the placebo group. Participants in both the treatment and placebo groups had improved scores on a number of psychological measures during the study. There was a correlation between perceived stress and weight change. CONCLUSION: The results of this pilot clinical study indicate that obese subjects who eat in response to stress may benefit from taking a dietary supplement ingredient containing proprietary extracts of M officinalis and P amurense. The mechanism of action appears to be through reduction of cortisol levels and possibly perceived stress, thereby helping participants maintain body weight. The sample size was small, however, and there was higher attrition in the control group than in the treatment group.

Dietary supplements: important concerns for the clinician.

Review articles, clinical trials and case reports on the usage patterns of dietary supplements are commonly published in medical journals. However, clinicians must acknowledge several limitations and methodological flaws with some of the available literature. The lack of product quality control, the use of combination products, and the paucity of product bioavailability data are known weaknesses of this research. Botanical dietary supplements present additional challenges to good quality research. Many factors impact the chemical composition of plants and, thus, influence the constituents in a manufactured product. Furthermore, the use of a validated and accurate product analysis technique is imperative to research on dietary supplements. This article discusses these topics in detail with special emphasis on those issues most important to practicing clinicians.

Assessment of the quality of reference books on botanical dietary supplements.

OBJECTIVE: To review books on botanical dietary supplements (BDS) targeted to pharmacists and physicians to assess their overall quality as primary and secondary reference books. DESIGN: We purchased 52 books for initial review based primarily on their titles. After eliminating books not written for health care professionals and books that contained very limited information on BDS, we selected 22 texts to review in depth. PARTICIPANTS: The review team consisted of four pharmacists--two with PhDs in pharmacognosy, one with a PhD in pharmaceutics, and one with a PharmD who is a senior medical student. RESULTS: The authors, reviewers, and editors of some books were highly qualified; others lacked the qualifications to summarize scientific information in a balanced, unbiased manner. Many books contain unsubstantiated statements. The books judged to be of the highest quality provide primary references to support all statements and advise the reader that insufficient information is available to assess potential drug interactions and safety during pregnancy and lactation. CONCLUSION: The quality of the information presented in the reviewed books varies dramatically. The most critical information gaps include the potential for drug interactions and the safe use of specific botanicals during pregnancy and lactation.