Development of microparticles and microparticulated tablets containing piperine

Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.

Eccema de contacto por extracto de pimienta negra como tratamiento de vitíligo / Contact Dermatitis Due to Black Pepper Extract Used to Treat Vitiligo

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Acute effects of mustard, horseradish, black pepper and ginger on energy expenditure, appetite, ad libitum energy intake and energy balance in human subjects.

Chilli peppers have been shown to enhance diet-induced thermogenesis (DIT) and reduce energy intake (EI) in some studies, but there are few data on other pungent spices. The primary aim of the present study was to test the acute effects of black pepper (pepper), ginger, horseradish and mustard in a meal on 4 h postprandial DIT. The secondary aim was to examine the effects on subjective appetite measures, ad libitum EI and energy balance. In a five-way placebo-controlled, single-blind, cross-over trial, twenty-two young (age 24·9 (SD 4·6) years), normal-weight (BMI 21·8 (SD 2·1) kg/m²) males were randomly assigned to receive a brunch meal with either pepper (1·3 g), ginger (20 g), horseradish (8·3 g), mustard (21 g) or no spices (placebo). The amounts of spices were chosen from pre-testing to make the meal spicy but palatable. No significant treatment effects were observed on DIT, but mustard produced DIT, which tended to be larger than that of placebo (14 %, 59 (SE 3) v. 52 (SE 2) kJ/h, respectively, P=0·08). No other spice induced thermogenic effects approaching statistical significance. Subjective measures of appetite (P>0·85), ad libitum EI (P=0·63) and energy balance (P=0·67) also did not differ between the treatments. Finally, horseradish decreased heart rate (P=0·048) and increased diastolic blood pressure (P= 0·049) compared with placebo. In conclusion, no reliable treatment effects on appetite, EI or energy balance were observed, although mustard tended to be thermogenic at this dose. Further studies should explore the possible strength and mechanisms of the potential thermogenic effect of mustard actives, and potential enhancement by, for example, combinations with other food components.

Black pepper and its pungent principle-piperine: a review of diverse physiological effects.

Black pepper (Piper nigrum) is one of the most widely used among spices. It is valued for its distinct biting quality attributed to the alkaloid, piperine. Black pepper is used not only in human dietaries but also for a variety of other purposes such as medicinal, as a preservative, and in perfumery. Many physiological effects of black pepper, its extracts, or its major active principle, piperine, have been reported in recent decades. Dietary piperine, by favorably stimulating the digestive enzymes of pancreas, enhances the digestive capacity and significantly reduces the gastrointestinal food transit time. Piperine has been demonstrated in in vitro studies to protect against oxidative damage by inhibiting or quenching free radicals and reactive oxygen species. Black pepper or piperine treatment has also been evidenced to lower lipid peroxidation in vivo and beneficially influence cellular thiol status, antioxidant molecules and antioxidant enzymes in a number of experimental situations of oxidative stress. The most far-reaching attribute of piperine has been its inhibitory influence on enzymatic drug biotransforming reactions in the liver. It strongly inhibits hepatic and intestinal aryl hydrocarbon hydroxylase and UDP-glucuronyl transferase. Piperine has been documented to enhance the bioavailability of a number of therapeutic drugs as well as phytochemicals by this very property. Piperine's bioavailability enhancing property is also partly attributed to increased absorption as a result of its effect on the ultrastructure of intestinal brush border. Although initially there were a few controversial reports regarding its safety as a food additive, such evidence has been questionable, and later studies have established the safety of black pepper or its active principle, piperine, in several animal studies. Piperine, while it is non-genotoxic, has in fact been found to possess anti-mutagenic and anti-tumor influences.

[Fat, spices and gastro-oesophageal reflux]. / Fette, Gewürze und gastroösophagealer Reflux.

In spite of poor evidence, many patients with gastro-oesophageal reflux are advised to avoid fat and spices. We therefore measured gastro-oesophageal reflux after fatty and spicy meals. During three 24-h pH monitoring sessions, eight volunteers ate two identical, low fat and mild beef stews, or a hot and fatty Indian curry for lunch. Meals for dinner were the beef stew, the hot Indian curry or a mild curry. Day-time acid exposure was significantly longer after the hot curry (7.5 % [1.4 - 27.1]) than after the beef stews (2.3 % [0.4 - 9.8] and 2.5 % [0.7 - 15.7]). Night-time acid exposure was also significantly shorter after the beef stew (1.3 % [0 - 9]) than after the mild curry (2.9 % [0 - 19.1]) or the hot curry (4.6 % [0.2 - 22.5]). Within two hours postprandially, reflux was not different between the meals. The number of episodes, however, that occurred more than two hours after lunch was significantly lower after the beef stews (4 [2 - 14] and 4.5 [2 - 10]) than after the hot curry (9 [5 - 16]). The same phenomenon was observed after beef stew (0.5 [0 - 2]), mild curry (2 [0 - 4]) and hot curry (2 [1 - 9]) for dinner. We conclude that meals high in fat can provoke reflux, possibly through delayed gastric emptying. Additional spices, however, do not further increase reflux.

Occupational rhinoconjunctivitis from white pepper.

A 44-year-old subject developed rhinoconjunctivitis symptoms when she was exposed to white pepper while working in the food industry. A positive skin prick test for white and black pepper extracts (1:10 w/v) were obtained. Specific IgE antibodies to white and black pepper were demonstrated by ELISA. The immunoblot analysis showed two IgE-reactive protein bands able to bind to IgE from white pepper extract of 11.8 kDa and 13.6 kDa and one band from black pepper extract of 11.8 kDa. IgE binding to blotted white and black pepper extract were inhibited by preincubation of patient serum with black pepper extract. A conjunctival provocation test was positive with a white pepper extract dilution of 1:100 w/v. We describe a patient with occupational rhinoconjunctivitis caused by hypersensitivity to white pepper.

Piperine in food: interference in the pharmacokinetics of phenytoin.

This study was carried out to explore the effect of piperine-containing food in altering the pharmacokinetics of phenytoin, an anti-epileptic drug with a narrow therapeutic index. A preliminary pharmacokinetic study was carried out in mice by administering phenytoin (10 mg) orally, with or without piperine (0.6 mg). Subsequently, oral pharmacokinetics of phenytoin was carried out in six healthy volunteers in a crossover design. Phenytoin tablet (300 mg) was given 30 minutes after ingestion of a soup (melahu rasam) with or without black pepper. A further study of intavenous pharmacokinetics of phenytoin (1 mg) in rats with or without oral pretreatment with piperine (10 mg) was also conducted. The phenytoin concentration in the serum was analyzed by HPLC. The study showed a significant increase in the kinetic estimates of Ka, AUC(0-10) and AUC(0-infinity) in the piperine-fed mice. Similarly, in human volunteers piperine increased Ka, AUC(0-48), AUC(0-infinity), and delayed elimination of phenytoin. Intravenous phenytoin in the oral piperine-treated rat group showed a significant alteration in the elimination phase indicating its metabolic blockade. The significance of this finding in epileptic patients maintained on phenytoin therapy requires further investigation. This study may also have implications in the case of other drugs having a low therapeutic index.