Development, characterization and viability study of probiotic microcapsules produced by complex coacervation followed by freeze-drying / Desenvolvimento, caracterização e estudo da viabilidade de microcápsulas probióticas produzidas por coacervação complexa seguida de liofilização

Technique of complex coacervation was used to produce microcapsules of Lactobacillus acidophilus La-5 encapsulated in gelatin and gum arabic which were then freeze-drying. Microcapsules were characterized using scanning electron and optical microscopy, and resistance of probiotics was evaluated during release into a simulated gastrointestinal tract and storage at different temperatures. The complex coacervation process produced microcapsules with a high encapsulation efficiency (77.60% and 87.53%), ranging from 127.14-227.05 m with uniform distribution. Microencapsulation was an efficient approach to achieve significant protection of probiotics against simulated gastrointestinal conditions compared with free cells. Encapsulation also improved the viability of probiotics during storage at either 18 ºC for 120 days, 7 ºC for 105 days or 25 ºC for 45 days. Therefore, complex coacervation was demonstrated to be adequate and promising for encapsulation of probiotics.(AU)

A técnica de coacervação complexa foi utilizada para a produção de microcápsulas contendo Lactobacillus acidophilus La-5 em gelatina e goma arábica seguida de secagem por liofilização. As microcápsulas foram caracterizadas por microscopia óptica e eletrônica de varredura, assim como a resistência dos probióticos frente à liberação in vitro ao trato gastrointestinal simulado e ao armazenamento em diferentes condições de temperatura também foram avaliados. O processo de coacervação complexa formou microcápsulas com alta eficiência de encapsulação (77,60% e 87,53%), tamanho compreendido entre 127,14 e 227,05 µm e distribuição uniforme. As microcápsulas foram eficientes em promover a proteção substancial dos probióticos frente às condições gastrointestinais simuladas, em comparação às células livres. A encapsulação também foi eficiente em manter a viabilidade dos probióticos durante o armazenamento em temperaturas de 18 ºC por 120 dias, 7 ºC por 105 dias e 25 ºC por 45 dias. Dessa forma, a coacervação complexa se mostra adequada e promissora para a encapsulação dos probióticos.(AU)

Oral administration of exogenous lactase in tablets for patients diagnosed with lactose intolerance due to primary hypolactasia / Administração oral de lactase exógena em comprimidos em pacientes portadores de intolerância à lactose devido à hipolactasia primária

ABSTRACT Background Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. , Objective Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

RESUMO Contexto A hipolactasia primária é uma condição muito frequente na qual há redução da atividade da lactase na mucosa intestinal.A presença de sintomas abdominais devidos à má absorção da lactose presente em alguns casos caracteriza a intolerância à lactose. Objetivo Avaliar a eficácia de um produto contendo lactase exógena em comprimidos comparativamente a de um produto comparador com eficácia comprovada em pacientes portadores de intolerância à lactose. Métodos Estudo multicêntrico, randomizado, de grupos paralelos, com investigador cego, comparativo de não-inferioridade. Cento e vinte e nove (129) pacientes adultos portadores de intolerância à lactose e teste do hidrogênio no ar expirado compatível com o diagnóstico de hipolactasia foram randomizados para receber o produto experimental (Perlatte(r) - Eurofarma Laboratórios S.A.) ou o produto comparador (Lactaid(r) - McNeil Nutritionals, EUA), por via oral (um comprimido, três vezes ao dia), durante 42 dias consecutivos. Resultados Os dados dos 128 pacientes que efetivamente receberam o tratamento do estudo foram avaliados (66 tratados com o produto experimental e 62 com o produto comparador). Os dois grupos se mostraram homogêneos quanto aos dados demográficos e clínicos basais. A média da concentração do hidrogênio expirado aos 90 minutos no teste realizado ao final do tratamento (Dia 42) foi significativamente menor no grupo tratado com o produto experimental (17±18 ppm versus 34±47 ppm na população por protocolo). A diferença entre as médias dos dois grupos foi de -17 ppm (intervalo de confiança de 95% [IC95%]: -31,03; -3,17). O limite superior do IC95% não ultrapassou a margem de não-inferioridade estipulada a priori (7,5 ppm). As análises secundárias de eficácia confirmaram a semelhança entre os tratamentos (populações por protocolo e com intenção de tratamento). A tolerabilidade foi excelente em ambos os grupos e não houve relato de eventos adversos graves relacionados ao produto. Conclusão O produto experimental se mostrou não-inferior ao produto comparador, indicando sua eficácia no tratamento substitutivo da lactase endógena em pacientes portadores de intolerância à lactose.

ORAL ADMINISTRATION OF EXOGENOUS LACTASE IN TABLETS FOR PATIENTS DIAGNOSED WITH LACTOSE INTOLERANCE DUE TO PRIMARY HYPOLACTASIA.

Background: Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. Objective: Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods: Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results: Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion: The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

Beneficial effects of long-term consumption of a probiotic combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult may persist after suspension of therapy in lactose-intolerant patients.

BACKGROUND: The efficacy of some probiotic strains for the management of lactose intolerance remains to be established. AIM: To evaluate the effects of a 4-week consumption of a probiotic product containing Lactobacillus casei Shirota and Bifidobacterium breve Yakult (10(7)-10(9) CFU of each strain) on symptoms and breath hydrogen exhalation after a lactose load in lactose-intolerant patients and whether the beneficial results persisted after probiotic discontinuation. METHODS: Twenty-seven patients with lactose maldigestion and intolerance participated in this study, which comprised 4 hydrogen breath tests: baseline condition (20 g lactose), after lactase ingestion (9000 FCC units), at the end of 4-week probiotic supplementation, and a follow-up test performed 3 months after probiotic discontinuation. For each test, the area under the breath hydrogen concentration vs time curve (AUC(180 min)) was calculated, and symptom scores were recorded. RESULTS: The probiotic combination significantly reduced symptom scores (P < .01) and breath hydrogen AUC (P = .04) compared with the baseline condition. The comparison with the lactase test showed that symptom scores were similar (P > .05), despite the significantly higher (P = .01) AUC values after probiotic use. In the follow-up test, symptom scores and breath hydrogen AUC values remained similar to those found at the end of probiotic intervention. CONCLUSION: Four-week consumption of a probiotic combination of L casei Shirota and B breve Yakult seems to improve symptoms and decrease hydrogen production intake in lactose-intolerant patients. These effects may persist for at least 3 months after suspension of probiotic consumption.

Probióticos / Probiotics

Los Probióticos son agentes terapéuticos biológicos emergentes, con utilidad probada en diarrea asociada a antibióticos, diarrea en la infancia y del viajero. Hay trabajos recientes que cifran esperanzas en la terapia de la diarrea asociada a C. difficile, en enfermedad inflamatoria intestinal, (tanto en tratamiento agregado a la terapia convencional de la crisis, como en la prevención de rebrotes). Por su excelente tolerancia, disponibilidad y acepatación por la población, debe considerarse dentro del recetario gastroenterológico con interés y expectación