Regular Lactose Research Articles

Adult lactose digestion status and effects on disease.

Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes. To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions. A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic. The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide. The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases. Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.

Dietary management of childhood diarrhea in low- and middle-income countries: a systematic review

BackgroundCurrent WHO guidelines on the management and treatment of diarrhea in children strongly recommend continued feeding alongside the administration of oral rehydration solution and zinc therapy, but there remains some debate regarding the optimal diet or dietary ingredients for feeding children with diarrhea.MethodsWe conducted a systematic search for all published randomized controlled trials evaluating food-based interventions among children under five years old with diarrhea in low- and middle-income countries. We classified 29 eligible studies into one or more comparisons: reduced versus regular lactose liquid feeds, lactose-free versus lactose-containing liquid feeds, lactose-free liquid feeds versus lactose-containing mixed diets, and commercial/specialized ingredients versus home-available ingredients. We used all available outcome data to conduct random-effects meta-analyses to estimate the average effect of each intervention on diarrhea duration, stool output, weight gain and treatment failure risk for studies on acute and persistent diarrhea separately.ResultsEvidence of low-to-moderate quality suggests that among children with acute diarrhea, diluting or fermenting lactose-containing liquid feeds does not affect any outcome when compared with an ordinary lactose-containing liquid feeds. In contrast, moderate quality evidence suggests that lactose-free liquid feeds reduce duration and the risk of treatment failure compared to lactose-containing liquid feeds in acute diarrhea. Only limited evidence of low quality was available to assess either of these two approaches in persistent diarrhea, or to assess lactose-free liquid feeds compared to lactose-containing mixed diets in either acute or persistent diarrhea. For commercially prepared or specialized ingredients compared to home-available ingredients, we found low-to-moderate quality evidence of no effect on any outcome in either acute or persistent diarrhea, though when we restricted these analyses to studies where both intervention and control diets were lactose-free, weight gain in children with acute diarrhea was shown to be greater among those fed with a home-available diet.ConclusionsAmong children in low- and middle-income countries, where the dual burden of diarrhea and malnutrition is greatest and where access to proprietary formulas and specialized ingredients is limited, the use of locally available age-appropriate foods should be promoted for the majority of acute diarrhea cases. Lactose intolerance is an important complication in some cases, but even among those children for whom lactose avoidance may be necessary, nutritionally complete diets comprised of locally available ingredients can be used at least as effectively as commercial preparations or specialized ingredients. These same conclusions may also apply to the dietary management of children with persistent diarrhea, but the evidence remains limited.

Formulation and evaluation and terbutaline sulphate and beclomethasone dipropionate inhalation mixtures in the rotahaler device

We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs terbutaline sulphate and beclomethasone dipropionate have been used to assess the effect of the surface smoothing technique on aerosolised drug delivery. The ROTAHALER device and the Twin Impinger BP were used in the assessment. Drug deposited in the throat, stage 1 and stage 2 of the Twin Impinger BP was determined and used to assess the difference between commercial lactose and the modified lactose prepared. The respirable fraction obtained with inhalation mixtures containing the recrystallized lactose samples was higher compared with inhalation mixtures containing regular lactose BP.Keywords: Rotahaler device, terbutaline sulphate, beclomethasone dipropionate, inhalation mixtures, twin impinger BP, respirable fraction

The formulation and evaluation of salbutamol dry powder inhalation mixtures with the Rotahler device

Metered dose inhalers (MDIs) contain chlorofluorocarbons, widely known, to affect the environment adversely. These chemicals deplete the ozone layer. The use of dry powder inhalers is therefore in the ascendance to replace MDIs for delivery of medicines to the respiratory tract. In this study we have formulated dry powder inhalation mixtures containing salbutamol sulphate using recrystallised lactose or modified lactose prepared by a proprietary method to smoothen the surface texture of the lactose. The effect of the proprietary method used to smoothen the surface texture of the recrystallized lactose was evaluated with the ROTAHALERTM device and the Twin Impinger BP in deposition tests. The respirable fraction obtained was higher in inhalation mixtures containing the recrystallized lactose compared to those containing regular lactose used as basis for comparison.Keywords: formulation, salbutamol, evaluation, powder, inhalation, Rotahaler

The formulation and evaluation of Disodium cromoglycate dry powder inhaler mixtures using the Rotahaler device

Inhalation of drugs offers the opportunity to treat diseases of the respiratory tract. In this drug delivery mode, the use of dry powder inhalers is preferred compared to pressurized metered dose inhalers. Metered dose inhalers contain chlorofluorocarbons known to affect the environment adversely. In this study we have formulated inhalation mixtures containing disodium cromoglycate using modified lactose. The effect of a proprietary method used to smoothen the surface of the modified lactose used as carrier for drug in the inhalation mixtures was determined with the ROTAHALERTM device and the Twin Impinger Apparatus BP. The respirable fraction obtained was higher in inhalation mixtures containing modified lactose compared to mixtures containing regular lactose, the control.Keywords: dry powder inhalers, respirable fraction, disodium cromoglycate, Rotahaler device, Twin Impinger BPJournal of Pharmaceutical and Allied Sciences, Vol. 7 No. 3 (2010)

The formulation and evaluation of terbutaline sulphate and dry powder inhalation mixtures with the rotahaler device

The formulation of the dry powder inhalers generally involves the production and characterization of a powder suitable for respiratory deposition and the formulation with or without excipients in a device. The drug formulation consists of micronised drug/s or mixtures of drug/s and carrier. A flow aid may be an additional component of the drug formulation. The formulation is usually prepackaged in unit doses or as a bulk, from which portions are dispensed. Though there have been significant advances, especially in understanding the role of carrier properties on the aerosol performance of the drug, the exact mechanism of adhesion and drug liberation during aerosolization is still not clearly understood and is a major focus among researchers within the field. In this study we report the use of low rugosity lactose, productof controlled crystallization of this carrier, in the formulation of terbutaline sulphate dry powder inhaler. The respirable fraction or the amount of emitted terbutaline sulphate available for deposition in the lungs for therapeutic action is higher in inhalation mixtures containing this modified lactose compared to regular lactose BP used as basis for comparison. Keywords: Dry powder inhaler, terbutaline sulphate, modified lactose, Rotahaler device, respirable fraction

Correlation between Inertial Impaction and Laser Diffraction Sizing Data for Aerosolized Carrier-based Dry Powder Formulations

The purpose of the study was to determine whether the drug fine particle fraction (FPF) from different dry powder aerosol formulations measured by laser diffraction at a range of flow rates correlated with that measured by inertial impaction. Ten binary formulations were prepared containing 1.5% w/w salbutamol base or sulphate, blended with the sieved (63-90 microm) fraction of different sugars (regular lactose, spray-dried lactose, sorbitol, dextrose or maltose). A further six ternary formulations were prepared containing 1.5% w/w salbutamol sulphate, 97% coarse lactose (63-90 microm) and 1.5% micronised or intermediate-sized lactose (1-50 microm). The FPF particles (< 5 microm) of these formulations were measured by laser diffraction and inertial impaction at flow rates between 28.3 and 100 l min(-1). When only the particles with diameter < 60 microm obtained by laser diffraction were considered the FPF (< 5 microm) could be determined and this enabled the aerosolisation of all 16 blends to be feasibly compared at flow rates ranging from 28.3 to 100 l min(-1). A significant linear correlation was found between the fine fractions measured by laser diffraction and the salbutamol fine fractions determined by inertial impaction (r2 = 0.934). Such correlation was also confirmed for formulations containing added fine lactose. Particle size measured by laser diffraction under the employed conditions reflected the aerodynamic properties of the drug. Laser diffraction can be used as on-, in- and/or at-line measurements and controls for dry powder aerosol formulations.

The use of different grades of lactose as a carrier for aerosolised salbutamol sulphate

Five different grades of lactose namely, anhydrous lactose, medium lactose, regular lactose, lactose crystals and foremost lactose were fractionated under similar conditions to obtain a size range of 63–90 μm and were characterised using laser diffraction and time-of-flight particle sizing techniques, scanning electron microscopy, optical microscopy image analysis, thermal gravimetric analysis and differential scanning calorimetry. Each of these lactose fractions were then blended separately with micronised salbutamol sulphate in a ratio of 67.5:1 (w/w). The mixing uniformity and percentage recovery of salbutamol sulphate in the powder blends were analysed using a validated HPLC method. The deposition profiles of the drug were determined using a 5-stage liquid impinger after aerosolisation at 60 l min −1 via a Rotahaler. Despite the identical processing conditions, the lactose fractions were shown to differ in particle size, size distribution and concentrations of fine particles. The particles from each fraction also exhibited different surface textures and dissimilar DSC thermograms. However, all the blends of the lactose with salbutamol sulphate were found to have a relatively high uniformity of salbutamol sulphate content, as suggested by a coefficient of variation of less than 3.2%. Anhydrous and medium lactose produced a more efficient delivery of salbutamol sulphate when aerosolised from the Rotahaler in comparison to other grades of lactose. For example, the fine particle fraction (FPF) and fine particle dose (FPD) of drug from formulations containing anhydrous lactose were 13.4±4.2% and 57.3±17.6 μg, respectively, which were approximately two times higher than the respective values of the formulation containing regular lactose. Medium lactose resulted in drug FPF (7.9±2.7%) and FPD (32.4±11.8 μg), which were significantly (ANOVA P<0.05) higher than the same parameters obtained using lactose crystals, foremost lactose and regular lactose. More efficient drug delivery from anhydrous lactose may be partly attributed to the relatively higher concentration of fine lactose in this grade of carrier, although it showed a rougher surface than the other grades of lactose. However, the relatively high FPF of the drug from medium lactose may have been due to the relatively small mean particle size and smooth surface of the particles. Therefore, the source and grade of lactose may have a substantial effect on drug delivery from dry powder inhaler formulations and care should be taken in establishing appropriate quality control parameters when selecting an appropriate grade of carrier.

Colonic adaptation to daily lactose feeding in lactose maldigesters reduces lactose intolerance

We conducted blinded, controlled crossover studies to determine the effect of daily lactose feeding on colonic adaptation and intolerance symptoms. The initial study with nine lactose maldigesters showed a threefold increase in fecal beta-galactosidase activity after 16 d of lactose feeding. To determine the effects of this adaptation on breath hydrogen and intolerance symptoms, 20 lactose-maldigesting adults were randomly assigned to lactose or dextrose supplementation for 10 d (days 1-10), crossing over to the other period for days 12-21. The sugar dosage was increased from 0.6 to 1.0 g.kg-1.d-1, subdivided into three equal doses, by adjusting the dose every other day. Symptoms during lactose supplementation and comparison of symptoms during the lactose and dextrose feeding periods showed no significant differences. On days 11 and 22, challenge doses of lactose (0.35 g/kg) were administered after an overnight fast, and breath hydrogen and intolerance symptoms (abdominal pain, flatulence, and diarrhea) were carefully monitored for 8 h. Frequency of flatus passage and flatus severity ratings after the lactose challenge decreased 50% when studied at the end of the lactose period compared with the dextrose period. The sum of hourly breath-hydrogen concentrations (1-8 h) was significantly reduced after the lactose feeding period (9 +/- 38 ppm.h) compared with after the dextrose period (385 +/- 52 ppm.h, P < 0.001). We conclude that there is colonic adaptation to regular lactose ingestion and this adaptation reduces lactose intolerance symptoms.