ObjectivesThe penetration of hydrocortisone (HC) from six topical over-the-counter products along with one prescription cream through cultured normal human-derived epidermal keratinocytes (Epiderm™), mouse skin and synthetic nylon membrane was performed as well as the effect hydrating the skin by pre-washing was explored using the Upright Franz Cell.Method and ResultsPermeation of HC through EpiDerm™, mouse skin and synthetic membrane was highest with the topical HC gel formulation with prewash treatment of the membranes among seven products evaluated, 198 ± 32 µg/cm2, 746.32 ± 12.43 µg/cm2, and 1882 ± 395.18 µg/cm2, respectively. Pre-washing to hydrate the skin enhanced HC penetration through EpiDerm™ and mouse skin. The 24-hour HC released from topical gel with prewash treatment was 198.495 ± 32 µg/cm2 and 746.32 ± 12.43 µg/cm2 while without prewash, the 24-h HC released from topical gel was 67.2 ± 7.41 µg/cm2 and 653.43 ± 85.62 µg/cm2 though EpiDerm™ and mouse skin, respectively. HC penetration through synthetic membrane was ten times greater than through mouse skin and EpiDerm™. Generally, the shape, pattern, and rank order of HC diffusion from each commercial product was similar through each membrane.

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This study compared the disintegration times of three immediate-release pain-relief tablets, ibuprofen (200 mg), tramadol HCl (50 mg), and hydrocodone bitartrate-acetaminophen (5 mg/500 mg), in different beverages (milk, calcium-fortified orange juice, commercial iced coffee, and regular Coca-Cola) with those in water using the USP disintegration apparatus. A hybrid medium prepared by blending 640 mL fat-free or 2% milk at 5.0 ± 1.0 °C with 160 mL of 0.1 N hydrochloric acid (HCl) at 39.0 ± 0.5 °C was proposed to better mimic human gastric content after tablet ingestion. The hybrid preparation was then used as the medium in USP dissolution Apparatus 2 to test these pain medications. The results show that the delay of the hydrocodone bitartrate-acetaminophen tablet disintegration in the hybrid media was less extensive than in straight milk (16.46 ± 0.65 min, n = 3 versus 31.94 ± 2.26 min, n = 6 when fat-free milk was used). Significant foam formed in both straight and hybrid fat-free milk. There was less foaming when the same tests were conducted in the USP dissolution apparatus. The ascending and descending motion of a USP disintegration apparatus may facilitate ambient air contact with fat-free milk, resulting in foam formation. If also true in vivo, it reflects a potential problem of hindered drug absorption.

Dissolution methods are different for extended-release mesalamine capsules (pH 7.5 only) and delayed-release tablets (pH 1.4, 6.0, and 7.2). Mesalamine is used for the treatment of ulcerative colitis. The USP methods have several drawbacks in that they do not mimic gastrointestinal tract environments; tablets are removed from vessels to change dissolution medium; and neither method has been adopted to compare different formulations. This study proposed a method that reflects gastrointestinal transit time and pH, is easy to conduct, and may be used to test new delayed-or extended-release formulations and compare various dosage forms.

Abstract. Eutectic mixtures formed between active pharmaceutical ingredients and/or excipients provide vast scope for pharmaceutical applications. This study aimed at the exploration of the crystallization abilities of two eutectic mixtures (EM) i.e., lidocaine-tetracaine and lidocaine-camphor (1:1 w/w). Thermogravimetric analysis (TGA) for degradation behavior whereas modulated temperature differential scanning calorimetry (MTDSC) set in first heating, cooling, and second heating cycles, was used to qualitatively analyze the complex exothermic and endothermic thermal transitions. Raman microspectroscopy characterized vibrational information specific to chemical bonds. Prepared EMs were left at room temperature for 24 h to visually examine their crystallization potentials. The degradation of lidocaine, tetracaine, camphor, lidocaine-tetracaine EM, and lidocaine-camphor EM began at 196.56, 163.82, 76.86, 146.01, and 42.72°C, respectively, which indicated that eutectic mixtures are less thermostable compared to their individual components. The MTDSC showed crystallization peaks for lidocaine, tetracaine, and camphor at 31.86, 29.36, and 174.02°C, respectively (n=3). When studying the eutectic mixture, no crystallization peak was observed in the lidocaine-tetracaine EM, but a lidocaine-camphor EM crystallization peak was present at 18.81°C. Crystallization occurred in lidocaine-camphor EM after being kept at room temperature for 24 h, but not in lidocaine-tetracaine EM. Certain peak shifts were observed in Raman spectra which indicated possible interactions of eutectic mixture components, when a eutectic mixture was formed. We found that if the components forming a eutectic mixture have crystallization peaks close to each other and have sufficient hydrogen-bonding capability, then their eutectic mixture is least likely to crystallize out (as seen in lidocaine-tetracaine EM) or vice versa (lidocainecamphor EM).

Background Insulin when stored according to manufacturers' recommendations offer at least 28 days of use after opening. A realistic understanding of room temperature storage at home includes exposure to heat and light. Pharmacy refill data suggest that patients tend to use opened insulin beyond 28 days. Insulin quality could be effected after 28 days when stored under uncontrolled conditions. Aim To evaluate the stability of two long‐acting insulin formulations, Humulin 70/30 and Levemir, after 28 days. Method A high‐performance liquid chromatography assay was used to quantify insulin area under the curve (AUC) profiles as an indicator of insulin quality. Human recombinant insulin (Humulin) 70/30 and insulin detemir (Levemir) vials were stored in refrigerated (2–8 °C, 36–46 °F) and room temperature (22–24 °C, 72–75 °F) conditions for up to 42 days, emulating patient managed storage and use patterns. Samples were taken on opening (time 0) and vials were randomised and stored in refrigerated or at room temperature conditions. Samples were taken and evaluated at Days 7, 14, 21, 28, 35 and 42. Results Humulin 70/30 and Levemir generated chromatograms with characteristic peaks at 12 and 21 minutes. Refrigerated Humulin 70/30 and Levemir AUCs were compared to time 0 and no differences were found. By Day 35, some Humulin 70/30 samples at room temperature had changes in AUC (p = 0.002) and loss of symmetry when compared to time 0 and all samples at Day 42 had changes in AUC (p < 0.0001). A similar pattern occurred with Levemir; some samples at room temperature had changes in AUC (p = 0.005) and loss of symmetry when compared to time 0 and all samples at Day 42 had changes in AUC (p < 0.0001). Conclusion Room temperature storage may effect Humulin 70/30 and Levemir AUCs and chromatograms by Day 42. Patients should be advised to store insulin in the refrigerator when possible and reminded that insulin quality can be effected by room temperature storage and beyond date use.

Background: Preparation of mini buccal tablets incorporating either of the Alzheimer's drugs, rivastigmine tartrate or donepezil hydrochloride, were developed for patients who have difficulty swallowing as a source of effervescence, by pairing the less commonly used malic acid with sodium bicarbonate in an experimentally determined (1:2) stochiometirc ratio. Methods: To avoid premature reaction of the acid and the base during compounding, the tablet ingredients were mixed in the following order: acid, sweetener, binder, drug, preservative, base, and anti-adherent/lubricant. Results: An accelerated thermal stability study at 40°C and 25% relative humidity showed that the integrity of the effervescent tablets containing rivastigmine tartrate were superior to that of donepezil HCl tablets. FT-IR spectrometry confirmed the presence of water of hydrate in donepezil HCl crystals. This water was absent in the IR after one-month storage at accelerated thermal stability, but was present at room temperature. This behavior was not observed in the tablet made from rivastigmine tartrate powder. Differential scanning calorimetry of donepezil hydrochloride showed two thermal events: the first was associated with the loss of the water, and the second, at much higher temperature, was the melting of theanhydrous drug. Such behavior was not observed in the rivastigmine tartrate powder. Conclusions: Hidden water which may function as catalyst to induce premature effervescence during storage.

Summary. The influence on the emergency caesarean section rate of 24‐h supervisory staff coverage in the labour and delivery area was investigated. In period I (1978–1979), the supervisory staff were inside the hospital from 07.01 to 17.00 hours, and on call at home from 17.01 to 07.00 hours of the next day, and in period I1 (1980–1981), the supervisory staff were inside the hospital 24 h a day. The section rate for fetal distress increased during period II. The rate for maternal complications also increased in the 17.01–24.00 hours shift and decreased in the 07.01–17.00 hours shift during period 11. However, the overall emergency caesarean section rate did not change between the two periods.