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According to current international Good Manufacturing Practice guidelines, ongoing stability testing is required for the market-life of all medicinal licensed products, as part of the Annual Product Quality Review. Taking that into account, samples from one batch a year of the three Policosanol formulations (PPG 5, 10 and 20 mg), stored in Climatic Zone IV conditions, were continuously monitored since 2017, in order to demonstrate stability and quality over their 5-years shelf life. Results showed that these three formulations, packed in polyvinylchloride /aluminium thermo-sealed blisters, fulfilled the specified quality parameters during all the study. Until now, all the assayed batches maintained their values of fatty alcohol content, uniformity of content, disintegration time, color, and microbial content without significant changes with respect to the initial values in all samplings. No evidence of degradation product formation was determined by Gas Chromatography, which is consistent with the fact that no decrease in the fatty alcohol content was observed throughout the study. First included batches, produced in 2017 and stored for five years, showed no evidence of degradation and fulfilled all the specification limits defined in their registration documents. That is consistent with the approved labelled shelf life of these formulations, which had been previously determined by Research and Development studies, before their marketing approval. [ABSTRACT FROM AUTHOR]

A new skin protective cream was recently developed containing the fatty alcohols 1-octacosanol (C28) and 1-triacontanol (30), which present antioxidant and anti-inflammatory properties. As part of the development of this new product, a Gas Chromatographic analytical method was validated. This method was used for the analyses of samples from three batches of the cream, which were submitted to accelerated stability assay during 12 months and to long-term stability assay during 36 months. The cream samples, packed at the rate of 25 g in lithographed aluminum tubes with inner epoxy-phenolic coating and high density polyethylene cap, were placed at 40 ± 2 ºC and 75 ± 5 % relative humidity (accelerated stability), and at 30 ± 2 ºC and 70 ± 5 % relative humidity (long-term stability in climatic Zone IV). The validated analytical method allowed to demonstrate that the fatty alcohols content did not change during all the time in which the samples were analyzed, in both assays.Additionally, it was observed that during all the time, the creams kept their original organoleptic characteristics (semi-solid with a uniform appearance, without lumps or sandy consistency, with a white to light cream color and a characteristic odor), as well as their microbiological content and pH between the Quality Specification defined ranges. The results of the present study support that the cream resist 12 months in conditions of accelerated stability and 36 months when stored at the conditions of the climatic Zone IV. [ABSTRACT FROM AUTHOR]

Palms have a wide distribution in tropical and subtropical regions, and are a promising source of substances for different uses. In Cuba they have been little studied and the Syagrus romanzoffiana palm is used as an ornamental plant for its beautiful leaves, as feathers and its rapid growth. In this work, the yields and the fatty acid content of the oils obtained from the whole fruits, seeds and pulps of the S. romanzoffiana palm were determined. The collected fruits were disinfected, dried and in half the seed was separated from the rest of the fruit (pulp). Whole fruits, seeds and pulps were ground separately to particle sizes <2.36 mm and the oils were obtained by extraction in Soxhlet with hexane. The oil with the highest yield (42%) and total fatty acid content (86% determined by Gas Chromatography) was obtained from the seeds. In all three oils there was a higher proportion of saturated fatty acids than unsaturated fatty acids. The highest percentages of saturated (70.5%) and unsaturated (41.3%) fatty acids in seed and pulp oils, respectively, were obtained. Lauric, oleic, myristic and palmitic acids were among the majority and arachidic, palmitoleic and linolenic acids were found among minorities. The present work allowed to know the extraction yields and the fatty acid contents of the oils obtained from the complete fruits, seeds and pulps of the S. romanzoffiana palm collected in Cuba. Such knowledge could encourage the cultivation of this palm as a possible source of oi ls for industrial use such as biodiesel or for human consumption, among others. [ABSTRACT FROM AUTHOR]

The D-004 is an active ingredient obtained from the fruits of the Cuban royal palm (Roystonea regia). It is mainly composed by a mixture of free fatty acids between 8 and 18 carbon atoms, with potential use in the treatment of the benign prostatic hyperplasia. Although batches of this substance, obtained at laboratory scale and packed in amber glass flasks, demonstrated to have a shelf life of 24 months in zones IV and II, the increase of its production to pilot scale demanded new studies that allowed defining the shelf life of batches obtained under the new conditions. Three pilot batches, packed in amber glass flasks, were stored in cardboard boxes under conditions of temperature and humidity corresponding to climatic zones IV (30 ºC/70 % RH) and II (25 ºC/ 60 % RH), and from the initial time until 51 months, quality parameters in samples randomly selected were determined. It was demonstrated that D-004 active ingredient obtained at pilot scale, under these storage conditions, maintained the following parameters: oleaginous liquid greenish brown color as organoleptic characteristics, contents of unsaponifiable matter between 1.2 and 2.7%, content of fatty acids between 86.6 and 95.4%, and the microbiological content specified by the international organisms for this kind of product. In this way, it was demonstrated that D-004 fulfilled their quality specifications during times that exceeded those obtained with laboratory batches. This investigation allowed determining that the studied active ingredient presents shelf lives of 33 and 48 months in the climatic zones IV and II, respectively. [ABSTRACT FROM AUTHOR]

Nowadays, the pharmaceutical regulatory entities are paying special attention to the topic of the residual solvents in the active ingredients (AI). D-004 is a new AI obtained from the Cuban royal palm (Roystonea regia) fruits, which has been shown to be effective in experimental models of prostate hyperplasia. Taking into account the use of n-hexane for obtaining this AI, a new limit test method, based on Static Headspace/GC-MS (SHS/GC-MS), was developed and validated for determining this residual solvent. six batches of D004 were used. For preparing samples, 1 mL of D-004 was placed into 10 mL vial and heated at 80 oC for 1 hour. Afterwards, 1 mL of the head space was immediately injected into the GC-MS. The n-hexane concentrations were determined by interpolating the n-hexane average responses in the calibration curve of the linearity test and limit concentration was established at 60 ppm. The proposed method for determining n-hexane as residual solvent in D004 AI was found suitable sensitive, specific, linear (correlation coefficient≥ 0.999 and R.S.D. of slope ≤ 2.4 %) and precise (RSD ≤ 8 %). Concentrations between 1.6 and 52 ppm were determined with a detection limit of 0.26 ppm. The validated limit test method allowed determining residual n-hexane concentrations, which were < 60 ppm, values that were lower than that established by the ICH (290 ppm). The method was found suitable for quality control of residual n-hexane in D004 AI. [ABSTRACT FROM AUTHOR]

In the last years, special attention has been paid to the pharmacological effects of very long chain fatty acids (VLCFA). Beeswax is considered safe for human consumption and constitutes an attractive source of VLCFA. Because of that; the aim of this paper was to obtain a VLCFA mixture from such crude wax. To do that, the wax was initially submitted to saponification; after that, Soxhlet extraction and successive purifications with organic solvents were carried out. The obtained mixture was characterized by its organoleptic and physical properties, as well as by the spectroscopic data (IR and GC-MS). The process yielded 5.9 % with good reproducibility (CV = 3.4 %), and the obtained substance was a white crystalline powder with a melting point ranging from 74 to 77 °C. It was composed, in around 90 %, of nine VLCFA in defined proportions: C16:0 (0.4 %), C22:0 (1.1 %), C24:0 (32.7 %), C26:0 (13.1 %), C28:0 (13.2 %), C30:0 (10.7 %), C32:0 (8.3 %), C34:0 (8.2 %), C36:0 (1.4 %), where C24:0 is the major component. Other compounds, detected in low concentrations, were VLCFA with odd carbon atoms (C25:0, C27:0, C29:0, C31:0) and unsaturated (C32:1, C34:1, C36:1), paraffins (C27, C29, C31), alcohols (C24-C34), (ω-1 hydroxy acids (C22:0, C24:0, C26:0) and α-(ω-1) diols (C26-C30). The reproducibility and yielding of the obtaining process, as well as the purity and quantity reached of this VLCFA mixture; allow its future possible pharmacological evaluation. [ABSTRACT FROM AUTHOR]

Policosanol is a cholesterol-lowering and antiplatelet substance consisting of a mixture of eigth higher aliphatic primary alcohols purified from sugarcane (Saccharum officinarum, L.) wax, whose relative composition supports its identity, and their total content the purity of the active ingredient. Policosanol identity and purity are reproducible, being the most outstanding quality specifications for the batch approval of the active ingredient or tablets. The efficacy, safety, and tolerability of policosanol have been extensively studied, the substance and drug products used in these studies responding to the quality specifications established. Recently, however, different mixtures of aliphatic alcohols, referred as .policosanols,. are in several markets, referring their claims to the evidences obtained with the original policosanol. Nevertheless, previous data support that different mixtures of such alcohols induce different biological responses. Then, here are compared the compositions of some .copycat-policosanol.: three active ingredients and 25 drug products, with that of genuine policosanol. Samples were processed according to the validated Gas Chromatographic methods used in the quality control of policosanol. None of the three active ingredients met policosanol identity and purity, the most striking discrepancy being referred to the identity, since the relative proportions of at least four alcohols were out of specifications (OOS), and some alcohols absent. Evident discrepancies were also found in the finished products, since only six complied with declared content of alcohols, many deviations being gross. No case reached the identity criterion, several alcohols being OOS, and some altogether missing. Differences rather than equivalence were detected after the analyses of both active ingredients and finished forms containing copycat- policosanols, leading to expected differences in their effects. Thus, copycat- policosanols deserve independent research to demonstrate their efficacy and safety, instead of formulating claims without supportive data. [ABSTRACT FROM AUTHOR]

Identification of hexacosanyl, octacosanyl, and triacontanyl stearates and palmitates as main thermal degradation products of policosanol in film-coated tablets containing 20 mg of this active ingredient was achieved by Gas Chromatography-Mass Spectrometry. In order to quantify these degradation products, a Gas Chromatographic method with flame ionisation detector, and docosanyl stearate as internal standard was developed and validated. In this method it was used a BPX-5 wide-bore capillary column (25 m X 0.53 mm d.i. X 1.0 µm of film thickness) in a temperature program from 300 to 350 °C . Validation of the method showed that it is accurate and linear in a range from 2.5 to 30 % of degradation. Precision studies of this method: repeatability and intermediate precision, assayed with tablets degraded in a 7.2 %, showed coefficients of variation lower than 2 %. Determined limits of detection and quantification (0.006 and 0.022 mg, respectively), determined for hexacosanyl palmitate, one of the minority degradation products, prove that the method can be used even for tablets with less than 2 % of degradation. Good accuracy and precision were obtained when tablets spiked with concentrations of hexacosanyl palmitate that correspond to the quantification limit were analyzed. The method is suitable in support of stability studies of these tablets. [ABSTRACT FROM AUTHOR]

A compilation of the studies carried out in the Center of Natural Products of the National Center for Scientific Research about the obtaining of crude oil from 11 species of palms (Arecaceae) that grow in Cuba (Veitchia merrillii, Caryota urens, Wodyetia bifurcata, Serenoa repens, Thrinax radiata, Roystonea regia, Colpothrinax wrightii, Sabal maritima, Sabal palmetto, Ptychosperma elegans and Livistona chinensis) is presented. The yields of oil extraction from the ripe whole-fruits, dried and milled, were between 0.6% and 25.5%. Such oils were semisolids or oleaginous liquids of different tonalities of brown, with characteristic odors, lightly aromatic. These oils showed free fatty acids contents between 1.2 and 70.2 %, and total fatty acids contents between 58.4 and 89.7 %, with palmitic (9.2 - 52.2 %) and oleic (9.6 - 42.7 %) as the main acids. In all the oils lauric (0.6 - 44.3 %), myristic (0.5 - 22.4%), stearic (1.7 - 6.1%), linoleic (3.5 - 28.5 %) and linolenic (0.1 - 3.4%) acids were also present; while palmitoleic (0.1-3.7 %), caproic (0-2.2 %), caprilic (0.1-2.8 %), capric (0.1-2.5 %), pentadecanoic (0.1- 0.5 %), heptadecanoic (0.2-0.7 %), uneicosanoic (0.1-0.2 %), eicosenoic (0.1-0.3 %) and docosaenoic (0.1-0.2 %) acids only appeared in some ones. The showed results could motivate the cultivation and better use of several of these natural resources. [ABSTRACT FROM AUTHOR]

The oil extracted from the whole fruits of Cuban royal palm (Roystonea regia) could be used in the food or pharmaceutical industry for obtaining a new active ingredient; then, this study investigates the physicochemical characteristics and stability of this oil. Fatty acids composition was determined by gas chromatography and the other determinations by USP 27 official methods. Stability study was assessed in glass containers with rubber cap and aluminum seal, under climatic zone IV conditions (30 ± 2 ºC and 70 ± 5 % relative humidity) over two years. Relative density was between 0.874 and 0.970 g/mL, refractive index between 1.454 and 1.463, saponification value between 190.0 and 221.8, acid value between 5.2 and 26.4, iodine value between 47.8 and 55.8, and unsaponifiable matter content between 2.0 and 13.4 %. The fatty acids content was between 74.4 and 91.3 %. No significant variations were observed in physic, chemical and microbiological characteristics of the three oil batches studied over two years. In conclusion, some of the physical and chemical characteristics of the oil from R. regia whole fruits were determined. This oil is stable over two years in clear glass bottle with rubber cap and aluminum seal under climatic zone IV conditions. [ABSTRACT FROM AUTHOR]

A new validated gas chromatographic (GC) method using acetyl chloride as a derivatizing agent for determining policosanol's high molecular weight alcohols (policosanol's fatty alcohols; PFAs) in fish oil (FO) is described. Before derivatizing the alcohols, FO was subjected to a methylation reaction, and then the PFAs were isolated in a chloroform fraction by silica gel by column liquid chromatography. GC analysis was performed using a BPX-5 wide-bore column and 1-eicosanol as an internal standard. Validation assays applied to the method proved noninterference by a very complex mixture of the FO with PFAs, even for samples subjected to stress conditions. Good linearity [correlation coefficient >0.999, relative standard deviation (RSD) of the slope <1.3%, and RSD of the response factors <1.9% with no bias] and accuracy (average recovery from 100.6 to 102.2%) over a range of 28-142% of the nominal concentration were obtained. Within-day and intermediate precisions at the nominal dose (100%) were 1.7 and 2.9%, respectively. The method was successfully used to identify and quantitate the PFAs in FO.